Volume 99, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Tetanus remains a significant burden in many low- and middle-income countries. The tetanus toxin acts within the central nervous system and intrathecal antitoxin administration may be beneficial, but there are safety concerns, especially in resource-limited settings. We performed a pilot study to assess the safety and feasibility of intrathecal human tetanus immunoglobulin in five adults with tetanus before the conduct of a large randomized controlled trial. Intrathecal injection via lumbar puncture was given to all patients within a median 140 (range 100–165) minutes of intensive care unit (ICU) admission. There were no serious adverse effects associated with the procedure although three patients had probably related minor adverse events which resolved spontaneously. Median ICU length of stay was 14 (range 5–17) days. Two patients required mechanical ventilation and one developed a deep vein thrombosis. Within 240 days of hospital discharge, no patients died and all patients returned to work.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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  1. Woldeamanuel YW, Andemeskel AT, Kyei K, Woldeamanuel MW, Woldeamanuel W, , 2016. Case fatality of adult tetanus in Africa: systematic review and meta-analysis. J Neurol Sci 368: 292299. [Google Scholar]
  2. Kyu HH, Mumford JE, Stanaway JD, Barber RM, Hancock JR, Vos T, Murray CJL, Naghavi M, , 2017. Mortality from tetanus between 1990 and 2015 : findings from the global burden of disease study 2015. BMC Public Health 17: 179. [Google Scholar]
  3. Sherrington CS, , 1917. The serum treatment of experimental tetanus in monkeys. Trans R Soc Trop Med Hyg 11: 5468. [Google Scholar]
  4. Andrewes F, , 1917. On the intrathecal route for the administration of tetanus antitoxin. Lancet 189: 682686. [Google Scholar]
  5. Abrutyn E, Berlin JA, , 1991. Intrathecal therapy in tetanus. A meta-analysis. JAMA 266: 22622267. [Google Scholar]
  6. Kabura L, Ilibagiza D, Menten J, Van den Ende J, , 2006. Intrathecal vs. intramuscular administration of human antitetanus immunoglobulin or equine tetanus antitoxin in the treatment of tetanus: a meta-analysis. Trop Med Int Health 11: 10751081. [Google Scholar]
  7. Agarwal M, Thomas K, Peter JV, Jeyaseelan L, Cherian AM, , 1998. A randomized double-blind sham-controlled study of intrathecal human anti-tetanus immunoglobulin in the management of tetanus. Natl Med J India 11: 209212. [Google Scholar]
  8. Robert R, Rouffineau A, Cremault A, Baupie J, Pourrat O, Gill R, DP, 1984. Paraplegie reversible apres injection intrathecale de fortes doses de gammaglobulines humaines lors du traitement de tetanos de faible gravite. La Press Medicalle 13: 19471948. [Google Scholar]
  9. Rowbotham MC, , 2010. PAIN’s policy on the spinal administration of drugs. Pain 149: 415416. [Google Scholar]
  10. Miranda-Filho DDB, Ximenes RADA, Barone AA, Vaz VL, Vieira AG, Albuquerque VMG, , 2004. Randomised controlled trial of tetanus treatment with antitetanus immunoglobulin by the intrathecal or intramuscular route. BMJ 328: 615. [Google Scholar]
  11. National Cancer Institute, 2010. Common Terminology Criteria for Adverse Events. Available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed March 2018.
  12. Vakil B, Armitage P, Clifford R, Laurence DR, , 1979. Therapeutic trial of intracisternal human tetanus immunoglobulin clinical tetanus. Trans R Soc Trop Med Hyg 73: 579583. [Google Scholar]
  13. Turnbull DK, Shepherd DB, , 2003. Post-dural puncture headache: pathogenesis, prevention and treatment. Br J Anaesth 91: 718729. [Google Scholar]
  14. Späth PJ, Granata G, La Marra F, Kuijpers TW, Quinti I, , 2015. On the dark side of therapies with immunoglobulin concentrates: the adverse events. Front Immunol 6: 223. [Google Scholar]
  15. Malato A, Dentali F, Siragusa S, Fabbiano F, Kagoma Y, Boddi M, Gensini GF, Peris A, Crowther M, Napolitano M, , 2015. The impact of deep vein thrombosis in critically ill patients: a meta-analysis of major clinical outcomes. Blood Transfus 13: 559568. [Google Scholar]
  16. Udwadia FE, , 1994. Tetanus. Oxford, United Kingdom: Oxford University Press.
  17. Hill AD, Fowler RA, Pinto R, Herridge MS, Cuthbertson BH, Scales DC, , 2016. Long-term outcomes and healthcare utilization following critical illness—a population-based study. Crit Care 20: 76. [Google Scholar]
  18. Trieu HT, 2017. Long-term outcome in survivors of neonatal tetanus following specialist intensive care in Vietnam. BMC Infect Dis 17: 646. [Google Scholar]
  19. Ablett J, Ablett JJL, , 1967. Analysis and Main Experiences in 82 Patients Treated in the Leeds Tetanus Unit. Symposium on Tetanus in Great Britain 1967. Leeds, United Kingdom: Leeds General Infirmary, 1–10.
  20. Knaus WA, Draper EA, Wagner DP, Zimmerman JE, , 1985. APACHE II: a severity of disease classification system. Crit Care Med 13: 818829. [Google Scholar]
  21. Ferreira FL, Bota DP, Bross A, Mélot C, Vincent JL, , 2001. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 286: 17541758. [Google Scholar]
  22. Thwaites CL, 2006. Predicting the clinical outcome of tetanus: the tetanus severity score. Trop Med Int Heal 11: 279287. [Google Scholar]

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  • Received : 19 Feb 2018
  • Accepted : 23 Apr 2018
  • Published online : 18 Jun 2018

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