Forensic Pathology Reviews pp 121-144

Part of the Forensic Pathology Reviews book series (FPR, volume 6)

Sudden Death from Infectious Disease

  • James A. Morris
  • Linda M. Harrison
  • Robert M. Lauder


This chapter is concerned with sudden death in infancy, childhood and adult life. Most of the evidence for a causal role for infection in sudden death comes from studies of sudden unexpected death in infancy (SUDI) and therefore the section on SUDI and closely related conditions forms the largest part of the material presented. There is a convincing body of evidence that infection has a role in at least some cases of sudden infant death. More specifically, there is evidence, based on sound theoretical principles and supported by laboratory experiments, that some cases of sudden death can be caused by common bacterial toxins absorbed from mucosal surfaces or delivered as part of a transient bacteraemia. This idea, termed the common bacterial toxin hypothesis, is not proven beyond doubt, it remains an hypothesis, but it does offer a plausible explanation for many of the features associated with sudden death at all ages. One reason for concentrating on this idea is that we are now in a position to prove or disprove the hypothesis using the techniques of genomics and proteomics. But we will only succeed if those who perform necropsy examinations in cases of sudden death are fully conversant with the theoretical background and are ready to obtain the appropriate specimens. Large-scale studies of the mucosal microbial flora with proteomic analysis of the bacterial secretome and parallel proteomic analysis of fluids obtained at autopsy are required. This is big science requiring experts in many disciplines. The potential rewards from these studies in terms of understanding disease are considerable and it will put autopsy pathology back in its rightful place at the centre of clinical academic medicine.


Sudden death SUDI Infection Forensic pathology Autopsy 


  1. 1.
    Fleming P, Blair P, Bacon C et al (2000) Sudden unexpected deaths in infancy: The CESDI SUDI studies 1993–1996. The Stationery Office, LondonGoogle Scholar
  2. 2.
    Brook I (2003) Unexplained fever in young children: how to manage severe bacterial infection. BMJ 327:1094–1097PubMedCrossRefGoogle Scholar
  3. 3.
    Weber MA, Ashworth MT, Risdon RA et al (2008) The role of post-mortem investigations in determining the cause of sudden unexpected death in infancy (SUDI). Arch Dis Child 93:1048–1053PubMedCrossRefGoogle Scholar
  4. 4.
    Morris JA, Haran D, Smith A (1987) Hypothesis: common bacterial toxins are a possible cause of the sudden infant death syndrome. Med Hypotheses 22:211–222PubMedCrossRefGoogle Scholar
  5. 5.
    Morris JA, Harrison LM, Biswas J et al (2007) Transient bacteraemia: a possible cause of sudden life threatening events. Med Hypotheses 69:1032–1039PubMedCrossRefGoogle Scholar
  6. 6.
    Morris JA (1999) The common bacterial toxin hypothesis of sudden infant death syndrome. FEMS Immunol Med Microbiol 25:11–17PubMedCrossRefGoogle Scholar
  7. 7.
    Telford DR, Morris JA, Hughes P et al (1989) The nasopharyngeal flora in the sudden infant death syndrome. J Infect 18:125–130PubMedCrossRefGoogle Scholar
  8. 8.
    Gilbert R, Rudd P, Berry PJ et al (1992) Combined effect of infection and heavy wrapping on the risk of sudden unexpected infant death. Arch Dis Child 67:171–177PubMedCrossRefGoogle Scholar
  9. 9.
    Lee S, Barson AJ, Drucker DB et al (1987) Lethal challenge of gnotobiotic weanling rats with bacterial isolates from cases of sudden infant death syndrome (SIDS). J Clin Pathol 40:1393–1396PubMedCrossRefGoogle Scholar
  10. 10.
    Sayers NM, Drucker DB, Morris JA (1995) Lethal synergy between toxins of staphylococci and enterobacteria: implications for sudden infant death syndrome. J Clin Pathol 48:929–932PubMedCrossRefGoogle Scholar
  11. 11.
    Sayers NM, Drucker DB, Telford DR et al (1995) Effects of nicotine on bacterial toxins associated with cot death. Arch Dis Child 73:549–551PubMedCrossRefGoogle Scholar
  12. 12.
    Bell S, Crawley BA, Oppenheim BA et al (1996) Sleeping position and the upper airways bacterial flora; possible relevance to cot death. J Clin Pathol 49:170–172PubMedCrossRefGoogle Scholar
  13. 13.
    Harrison LM, Morris JA, Telford DR et al (1999) The nasopharyngeal bacterial flora in infancy: effects of age, gender, season, viral upper respiratory tract infection and sleeping position. FEMS Immunol Med Microbiol 25:19–28PubMedCrossRefGoogle Scholar
  14. 14.
    Zorgani A, Essery SD, Al Madani OA et al (1999) Detection of pyrogenic toxins of Staphylococcus aureus in sudden infant death syndrome. FEMS Immunol Med Microbiol 25:101–108CrossRefGoogle Scholar
  15. 15.
    Malam JE, Carrick GF, Telford DR et al (1992) Staphylococcal toxins and sudden infant death syndrome. J Clin Pathol 45:716–721PubMedCrossRefGoogle Scholar
  16. 16.
    Oppenheim BA, Barclay GR, Morris JA et al (1994) Antibodies to endotoxin core in sudden infant death syndrome. Arch Dis Child 70:95–98PubMedCrossRefGoogle Scholar
  17. 17.
    Blair PS, Platt MW, Smith IJ et al (2006) Sudden infant death syndrome and time of death: factors associated with night-time and day-time deaths. Int J Epidemiol 35:1563–1569PubMedCrossRefGoogle Scholar
  18. 18.
    Meny RG, Carroll JL, Carbone MT et al (1994) Cardiorepiratory recordings from infants dying suddenly and unexpectedly at home. Pediatrics 93:44–49PubMedGoogle Scholar
  19. 19.
    Poets CF, Meny RG, Chobanian MR et al (1999) Gasping and cardiorespiratory patterns during sudden infant deaths. Pediatrics 45:350–354CrossRefGoogle Scholar
  20. 20.
    Alouf JE, Freer JH (1991) The comprehensive source book of bacterial protein toxins. Academic Press, London, UKGoogle Scholar
  21. 21.
    Raza MW, Balckwell CC et al (1999) Sudden infant death syndrome, virus infections and cytokines. FEMS Immunol Med Microbiol 25:85–96PubMedCrossRefGoogle Scholar
  22. 22.
    Arnestad M, Crotti L, Rognum TO et al (2007) Prevalence of Long QT syndrome gene variants in sudden infant death syndrome. Circulation 115:361–367PubMedCrossRefGoogle Scholar
  23. 23.
    Levin M, Hjelm M, Kay LDS et al. (1983) Haemorrhagic shock and encephalopathy: a new syndrome with a high mortality in young children. Lancet ii:64–67Google Scholar
  24. 24.
    Bacon CJ, Scott D, Jones P (1979) Heatstroke in well wrapped infants. Lancet i:422–425Google Scholar
  25. 25.
    Bacon CJ, Bellman MH (1983) Heatstroke as a possible cause of encephalopathy in infants. BMJ 287:328PubMedCrossRefGoogle Scholar
  26. 26.
    Bacon CJ, Hall SM (1992) Haemorrhagic shock and encephalopathy syndrome in the British Isles. Arch Dis Child 67:985–993PubMedCrossRefGoogle Scholar
  27. 27.
    Morris JA (1983) Haemorrhagic shock and encephalopathy. Lancet ii:686Google Scholar
  28. 28.
    Bacon CJ, Bell SA, Gaventa JM et al (1999) Case control study of thermal environment preceding haemorrhagic shock encephalopathy syndrome. Arch Dis Child 81:155–158PubMedCrossRefGoogle Scholar
  29. 29.
    Van Lierde S, van Leeuwen WJ, Ceuppens J et al (1997) Toxic shock syndrome without rash in a young child: link with syndrome of haemorrhagic shock and encephalopathy. J Pediatrics 131:130–134CrossRefGoogle Scholar
  30. 30.
    McGovern MC, Smith MBH (2004) Causes of apparent life threatening events in infancy; a systematic review. Arch Dis Child 89:1043–1048PubMedCrossRefGoogle Scholar
  31. 31.
    Kiechl-Kohlendorfer U, Hof D, Peglow U et al (2005) Epidemiology of apparent life threatening events. Arch Dis Child 90:297–300PubMedCrossRefGoogle Scholar
  32. 32.
    Poets CF, Samuels MP, Noyes JP et al (1993) Home event recordings of oxygenation, breathing movements, and heart rate and rhythm in infants with recurrent life threatening events. J Pediatr 123:693–701PubMedCrossRefGoogle Scholar
  33. 33.
    Geddes JF, Hackshaw AK, Vowles JH et al (2001) Neuropathology of inflicted head injury in children: 1. patterns of brain damage. Brain 124:1290–1298PubMedCrossRefGoogle Scholar
  34. 34.
    Geddes JF, Vowles JH, Hackshaw AK et al (2001) Neuropathology of inflicted head injury in children: 2 Microscopic brain injury in infants. Brain 124:1299–1306PubMedCrossRefGoogle Scholar
  35. 35.
    Byard RW, Blumberg P, Rutty G et al (2007) Lack of evidence for a causal relationship between hypoxic-ischaemic encephalopathy and subdural haemorrhage in fetal life, infancy and childhood. Pediatric Develop Pathol 10:348–350CrossRefGoogle Scholar
  36. 36.
    Cohen MC, Scheimberg I (2008) Evidence of occurrence of intradural and subdural haemorrhage in the perinatal and neonatal perid in the context of hypoxic ischaemic encephalopathy. An observational study from two referral centres. Pediatr Dev Pathol. doi:10.2350/08-08-0509.1
  37. 37.
    Nei M (1987) Molecular evolutionary genetics. Columbia University Press, New YorkGoogle Scholar
  38. 38.
    Maynard-Smith J (1997) Evolutionary genetics, 2nd edn. Oxford University Press, OxfordGoogle Scholar
  39. 39.
    Drake JW, Charlesworth B, Charlesworth D et al (1998) Rates of spontaneous mutation. Genetics 148:1667–1686PubMedGoogle Scholar
  40. 40.
    Baltimore D (2001) Our genome unveiled. Nature 409:814–816PubMedCrossRefGoogle Scholar
  41. 41.
    Morris JA (2005) Synergistic interaction of heterozygous deletions impairs performance and confers susceptibility to disease at all ages. Med Hypotheses 65:483–493PubMedCrossRefGoogle Scholar
  42. 42.
    Summers AM, Summers CW, Drucker DB et al (2000) Association of IL-10 genotype with sudden infant death syndrome. Human Immunol 61:1270–1273CrossRefGoogle Scholar
  43. 43.
    Gordon AE, MacKenzie DAC, El Ahmer OR et al (2002) Evidence for a genetic component in sudden infant death syndrome. Child Care Health Dev 28(Suppl 1):27–29PubMedCrossRefGoogle Scholar
  44. 44.
    Korachi M, Pravica V, Barson AJ et al (2004) Interleukin-10 genotype as a risk factor for sudden infant death syndrome: determination of IL-10 genotype from wax embedded postmortem samples. FEMS Immunol Med Microbiol 42:125–129PubMedCrossRefGoogle Scholar
  45. 45.
    Moscovis SM, Gordon AE, Al Madani OM et al (2004) Interleukin-10 and sudden infant death syndrome. FEMS Immunol Med Microbiol 42:130–138PubMedCrossRefGoogle Scholar
  46. 46.
    Moscovis SM, Gordon AE, Hall ST et al (2004) Interleukin 1-beta responses to bacterial toxins and sudden infant death syndrome. FEMS Immunol Med Microbiol 42:139–145PubMedCrossRefGoogle Scholar
  47. 47.
    Blackwell CC, Moscovis SM, Gordon AE et al (2005) Cytokine responses and sudden infant death syndrome: genetic, developmental, and environmental risk factors. J Leukocyte Biol 78:1242–1254PubMedCrossRefGoogle Scholar
  48. 48.
    Dashash M, Pravica V, Hutchinson IV et al (2006) Association of sudden infant death syndrome with VEGF and IL-6 gene polymorphisms. Human Immunol 67:627–633CrossRefGoogle Scholar
  49. 49.
    Morris JA (2004) Common bacterial toxins and physiological vulnerability to sudden infant death: the role of deleterious genetic mutations. FEMS Immunol Med Microbiol 42:42–47PubMedCrossRefGoogle Scholar
  50. 50.
    Schwartz PJ, Crotti L et al (2008) Ion channel disease in children: manifestations and management. Curr Opin Cardiol 23:184–191PubMedCrossRefGoogle Scholar
  51. 51.
    Marita H, Wu J, Zipes DP (2008) The QT syndromes: long and short. Lancet 372:750–763CrossRefGoogle Scholar
  52. 52.
    Morris JA, Harrison LM, Brodison A et al (2009) Sudden infant death syndrome and cardiac arrhythmias. Future Cardiol 5:201–207PubMedCrossRefGoogle Scholar
  53. 53.
    Fishman RA (1992) Cerebrospinal fluid in diseases of the nervous system. W B Saunders, LondonGoogle Scholar
  54. 54.
    Platt MS, McClure S, Clarke R et al (1989) Postmortem cerebrospinal fluid pleocytosis. Am J Forens Med Pathol 10:209–212CrossRefGoogle Scholar
  55. 55.
    Wyler D, Marty W, Bar W (1994) Correlation between the postmortem cell content of cerebrospinal fluid and time of death. Int J Legal Med 106:194–199PubMedCrossRefGoogle Scholar
  56. 56.
    Morris JA, Harrison LM (2007) The microbiological investigation of sudden unexpected death in infancy. In: Kirkham N, Shepherd NA (eds) Progress in pathology. Cambridge University Press, CambridgeGoogle Scholar
  57. 57.
    Ehrlich P (1885) Das Sauerstoffbeduerfnis des Organismus. Eine farbenanalytische Studie, A Hirschfeld, BerlinGoogle Scholar
  58. 58.
    Mangin P, Lugnier AA, Chaumont AJ et al (1983) Forensic significance of postmortem estimation of the blood cerebrospinal fluid barrier permeability. Forens Sci Int 22:143–149CrossRefGoogle Scholar
  59. 59.
    Osuna E, Perez-Carceles MD (1992) Luna A (1992) Efficacy of cerebrospinal fluid biochemistry in the diagnosis of brain insult. Forens Sci Int 52:193–198CrossRefGoogle Scholar
  60. 60.
    Romeo MJ, Espina V, Lowenthal M et al (2005) CSF proteome: a protein repository for potential biomarker identification. Expert Rev Proteomics 2:57–70PubMedCrossRefGoogle Scholar
  61. 61.
    Maurer MH (2008) Proteomics of brain extracellular fluid (ECF) and cerebrospinal fluid (CSF). Mass Spectrom Rev. doi:10.1002/mas.20213
  62. 62.
    Blackstock WP, Weir MP (1999) Proteomics: quantitative and physical mapping of cellular proteins. Trends Biotechnol 17:121–126PubMedCrossRefGoogle Scholar
  63. 63.
    Pocsfalvi G, Cacace G, Cuccurullo M et al (2008) Proteomic analysis of exoproteins expressed by enterotoxigenic Staphylococcus aureus strains. Proteomics 8:2462–2476PubMedCrossRefGoogle Scholar
  64. 64.
    Kawano Y, Ito Y, Yamakawa Y et al (2000) Rapid isolation and identification of staphylococcal exoproteins by reverse phase capilliary high performance liquid chromatography-electrospray ionization mass spectrometry. FEMS Microbiol Lett 189:103–108PubMedGoogle Scholar
  65. 65.
    Nedelkov D, Nelson RW (2003) Detection of staphylococcal enterotoxin B via biomolecular interaction analysis mass spectrometry. Appl Environ Microbiol 69:5212–5215PubMedCrossRefGoogle Scholar
  66. 66.
    Callahan JH, Shefcheck KJ, Williams TL et al (2006) Detection, confirmation and quantification of staphylococcal enterotoxin B in food matrixes using liquid chromatography-mass spectrometry. Annal Chem 78:1789–1800CrossRefGoogle Scholar
  67. 67.
    Kientz C, Hulst AG, Wils ER (1997) Determination of staphylococcal enterotoxin B by on-line (micro) liquid chromatography-electrospray mass spectrometry. J Cromatogr A 757:51–64CrossRefGoogle Scholar
  68. 68.
    Morris JA, Harrison LM, Partridge SM (2006) Postmortem bacteriology: a re-evaluation. J Clin Pathol 59:1–9PubMedCrossRefGoogle Scholar
  69. 69.
    Weber MA, Klein NJ, Hartley JC et al (2008) Infection and sudden unexpected death in infancy: a systematic retrospective case review. Lancet 371:1848–1853PubMedCrossRefGoogle Scholar
  70. 70.
    Harrison LM, Morris JA, Lauder RM et al (2009) Staphylococcal pyrogenic toxins in infant urine samples; a possible marker of transient bacteraemia. J Clin Path 62:735–738PubMedCrossRefGoogle Scholar
  71. 71.
    Krous HF, Chadwick AE, Crandall L et al (2005) Sudden unexpected death in childhood: a report of 50 cases. Pediatr Dev Pathol 8:307–319PubMedCrossRefGoogle Scholar
  72. 72.
    Kinney KC, Armstrong DL, Chadwick AE et al (2007) Sudden death in toddlers associated with developmental abnormalities of the hippocampus: a report of five cases. Paediatr Dev Pathol 10:208–223CrossRefGoogle Scholar
  73. 73.
    Goldenberg I, Moss AJ, Peterson DR et al (2008) Risk factors for aborted cardiac arrest and sudden cardiac death in children with congenital long-QT syndrome. Circulation 117:2184–2191PubMedCrossRefGoogle Scholar
  74. 74.
    Hobbs JB, Peterson DR, Moss AJ et al (2006) Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long-QT syndrome. JAMA 296:1249–1254PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • James A. Morris
    • 1
  • Linda M. Harrison
    • 1
  • Robert M. Lauder
    • 2
  1. 1.Department of PathologyUniversity Hospitals of Morecambe Bay NHS TrustLancasterUK
  2. 2.Division of Biomedical and Life Sciences, School of Health and MedicineLancaster UniversityLancasterUK

Personalised recommendations