Evaluation of beneficial effects of addition of intramuscular human tetanus immunoglobulin to intrathecal therapy in the treatment of tetanus

Sanjiv Mahajan


Background: The treatment of tetanus has evolved from supportive management only to specific treatment to neutralize the tetanus toxins – tetanospasmin & tetanolysin. Human Tetanus Immunoglobulin (HTIg) is a large molecule and cannot cross the blood brain barrier. Introduction of intrathecal therapy considerably decreased mortality in the disease. Combined administration of intramuscular and intrathecal HTIg should neutralize the tetanus toxins in the circulation and central nervous system simultaneously. The study was done to detect beneficial effects of adding intramuscular HTIg to the intrathecal therapy.

Methods: 125 patients of tetanus were randomized to two groups. Study group was given intrathecal plus intramuscular HTIg while control group was given intrathecal HTIg alone. Each group was subdivided into three grades according to severity. Mortality rate and three sequential recovery parameters i.e. duration of spasms, shift to oral therapy and duration of hospital stay were measured.

Results: No significant difference in mortality was found. However, in patients who survived, the addition of intramuscular HTIg lead to a benefit of 2.07, 2.67 & 2.31 days in mild, moderate & severe grades respectively in the duration of spasms. Further, it became possible to start oral therapy 2.13, 1.6 & 1.8 days earlier in mild, moderate & severe tetanus. Duration of hospital stay was reduced by 3.87 days, 2.36 days and 3 days in mild, moderate and severe tetanus respectively.

Conclusions: Though the addition of intramuscular HTIg to intrathecal therapy in tetanus does not confer any survival benefit, it causes faster recovery in patients who survive.


Human tetanus immunoglobulin, Intramuscular, Intrathecal, Oral therapy, Spasms, Tetanus

Full Text:



Brodie BC. Experiments and observations on the different modes in which death is produced by certain vegetable poisons. Phil Trans Roy Soc. 1811;101:178-208.

O'Beirne J. Abstract of a communication on tetanus or locked-jaw. Lancet. 1836;26(680):826-7.

Von Behring E, Kitasato S. Ueber das Zustandekommen der Diphtherie-Immunität und der Tetanus-Immunität bei Thieren. Dtsch Med Wochenschr. 1890;16(49):1113-4.

Ramon G. Notice des titres et travaux scientifiques de G. Ramon, Paris. Ancienne imprimerie de la Cour d'Appel. 1934:109.

Ildirim I. A new treatment for neonatal tetanus - antitetanic serum and prednisolone given together intrathecally. The Turk J Pediatr. 1967;9:89-95

Sedaghatian MR. Intrathecal serotherapy in neonatal tetanus: a controlled trial. Arch Dis Child. 1979;54:623-5.

Vakil BJ, Armitage P, Clifford RE, Laurence DR. Therapeutic trial of intracisternal human tetanus immunoglobulin in clinical tetanus. Trans R Soc Trop Med Hyg. 1979;73:579-83.

Bhandari B, Ajmera NK, Jagetiya PR. Intrathecal antitetanus serum in management of tetanus neonatorum. Indian J Med Res. 1980;72:685-7.

Mongi PS, Mbise RL, Msengi AE, Do Amsi DM. Tetanus neonatorum – experience with intrathecal serotherapy at Muhimbili Medical Centre, Dar es Salaam, Tanzania. Ann Trop Paediatr. 1987;7:27-31.

Menon J, Mathews L. Intrathecal immunoglobulin in the treatment of tetanus. Indian Pediatr. 2002;39:654-7.

Miranda-Filho Dde B, Ximenes RA, Barone AA, Vaz VL, Vieira AG, Albuquerque VM. Randomised controlled trial of tetanus treatment with antitetanus immunoglobulin by the intrathecal or intramuscular route. BMJ. 2004;328:615-9.

Ahmad A, Qaisar I, Naeem M, Mazhar AU, Ashfaq M. Intrathecal antitetanus human immunoglobulin in the treatment of neonatal tetanus. J Coll Physicians Surg Pak. 2011;21:539-41.

Abrutyn E, Berlin JA. Intrathecal therapy in tetanus: A meta-analysis. JAMA. 1991;266:2262-7.

Kabura L, Ilibagiza D, Menten J, Van den Ende J. Intrathecal vs. intramuscular administration of human antitetanus immunoglobulin or equine tetanus antitoxin in the treatment of tetanus: A meta-analysis. Trop Med Int Health. 2006;11:1075-81.

Patel JC, Joag GG. Grading of tetanus to evaluate prognosis. Indian J Med Sci. 1959;13:834-40.

Agarwal M, Thomas K, Peter JV, Jeyaseelan L, Cherian AM. A randomized double-blind sham-controlled study of intrathecal human anti-tetanus immunoglobulin in the management of tetanus. Natl Med J India. 1998;11:209-12.

Robert R, Rouffineau J, Cremault A. Paraplegie reversible apre` injection intrathecale de fortes doses de gammaglobulines humaines lors du traitement de tetanos de faible gravite´. Quatre observations. La Presse Medicale. 1984;13:1947-79.