Tetanus

1. Tetanus Reşat ÖZARAS, MD., Prof. Infectious Dept.

2. Definition • Tetanus is a toxin-mediated infectious disease characterized by increased muscle tone and spasms • It is caused by tetanospasmin, a powerful protein toxin elaborated by Clostridium tetani.

3. Etiology-1 • C. tetani • anaerobic, motile gram-positive rod • forms a terminal spore: resembles a tennis racket. • The organism is found worldwide • in soil in animal feces, • occasionally in human feces.

4. Spores may survive for years in environments and are resistant to boiling for 20 min. • Vegetative cells, however, are easily inactivated and are susceptible to several antibiotics (metronidazole, penicillin, and others).

5. Etiology • Tetanospasmin is formed in vegetative bacteria under plasmid control. • It has a heavy chain, which mediates binding to nerve-cell receptors and entry into these cells, and a light chain, which acts to block neurotransmitter release.

6. Epidemiology • Tetanus occurs sporadically and always affects nonimmunized persons • Tetanus is entirely preventable by immunization • In countries without a comprehensive immunization program, tetanus occurs predominantly • in neonates and • young children; an estimated ~500.000 neonates died of tetanus worldwide in 1993.

7. Wound classification Clinical featuresTetanus proneNon-tetanus prone Age of wound >6 hours 6 hours Configuration Stellate Linear Depth >1 cm 1 cm Mechanism of injury Missile, crush Sharp surface burn,frostbite (glass, knife) Devitalized tissue Present Absent Contaminants Present Absent

8. Pathogenesis-1 • The injury may be major but often is trivial and, in some instances no injury can be identified. • Tetanus is also associated with burns, frostbite, surgery, abortion, and drug abuse • In some patients no portal of entry for the organism can be identified.

9. Pathogenesis-2 • Contamination of wounds with spores of C. tetani. • Germination and toxin production take place only in wounds with devitalized tissue • Toxin released in the wound binds to peripheral motor neuron terminals, enters the axon, and is transported to spinal cord by retrograde intraneuronal transport.

10. Pathogenesis-3 • The toxin then migrates across the synapse to presynaptic terminals, where it blocks release of the inhibitory neurotransmitters glycine and gamma-aminobutyric acid (GABA).

12. Clinical forms of tetanus • 1-Generalized tetanus • 2-Neonatal tetanus • 3-Local tetanus • 4-Cephalic tetanus

13. Generalized tetanus • The most common clinical form of the disease • Characterized by increased muscle tone and generalized spasms. • The median time of onset after injury is 7 days; • 15 percent of cases occur within 3 days and • 10 percent after 14 days. • Typically, the patient first notices increased tone in the masseter muscles (trismus, or lockjaw).

15. Generalized tetanus • Dysphagia, stiffness or pain in the neck, shoulder, and back muscles appears concurrently or soon thereafter. • The subsequent involvement of other muscles produces a rigid abdomen and stiff proximal limb muscles • The hands and feet are relatively spared. • Sustained contraction of the facial muscles results in a risus sardonicus • These spasms occur repetitively and may be spontaneous or provoked by even the slightest stimulation.

16. Contraction of the back muscles produces opisthotonos

17. Generalized tetanus • A constant threat during generalized spasms is reduced ventilation or apnea or laryngospasm. • The severity of illness may be mild (few or no spasms), moderate (trismus and dysphagia), or severe (frequent explosive paroxysms). • Patients have no fever • Mentation is unimpaired. • Deep tendon reflexes may be increased. • Dysphagia or ileus may preclude oral feeding.

18. Generalized tetanus • Autonomic dysfunction commonly complicates severe cases and is characterized by • labile or sustained hypertension, • tachycardia, • arrhythmia, • hyperpyrexia, • profuse sweating, • peripheral vasoconstriction, and • increased plasma and urinary catecholamine levels. • Other complications include pneumonia, fractures, muscle rupture, deep vein thrombophlebitis, pulmonary emboli, decubitus ulcer, and rhabdomyolysis.

19. Neonatal tetanus • It usually occurs as the generalized form • It is usually fatal if left untreated. • It develops in children born to inadequately immunized mothers, frequently after unsterile treatment of the umbilical cord stump. • Its onset generally comes during the first 2 weeks of life. • Poor feeding, rigidity, and spasms are typical features of neonatal tetanus.

21. Local tetanus • It is an uncommon form in which manifestations are restricted to muscles near the wound. • The prognosis is excellent.

22. Cephalic tetanus • A rare form of local tetanus, follows head injury • Trismus and dysfunction of one or more cranial nerves, often the seventh nerve, are found • The incubation period is a few days and the mortality is high.

23. Diagnosis • The diagnosis of tetanus is based entirely on clinical findings. • CSF fluid examination yields normal results • Muscle enzyme levels may be raised.

24. The differential diagnosis-1 • The differential diagnosis includes local conditions also producing trismus, such as 1-Abscess, 2- strychnine poisoning, 3-dystonic drug reactions (such as phenothiazines and metoclopramide), 4-tetany.

25. The differential diagnosis-2 • Other conditions sometimes confused with tetanus include; 1-meningitis 2-rabies, and 3-an acute intraabdominal process (because of the rigid abdomen).

26. The differential diagnosis-3 • Markedly increased tone in central muscles (face, neck, chest, back, and abdomen) with superimposed generalized spasms and relative sparing of the hands and feet strongly suggests tetanus.

27. Treatment; the goals of therapy 1-To eliminate the source of toxin, 2-Neutralize unbound toxin, 3-Prevent muscle spasms, 4-Provide support¾especially respiratory support¾until recovery. 5-Patients should be admitted to a quiet room in an intensive care unit 6-Cardiopulmonary monitoring can be maintained continuously 7-Stimulation can be minimized 8-Protection of the airway is vital. 9- Wounds should be cleansed, and thoroughly debrided.

28. Antibiotic therapy • Penicillin; 12 million units iv/day-10 days • Metronidazole; 500 mgx4or 1 gx2/day and the absence of the GABA antagonistic activity seen with penicillin. • Clindamycin is alternative for the treatment of penicillin-allergic patients.

29. Antitoxin • Human tetanus immune globulin (TIG); ~5000 U IM, usually in divided doses because the volume is large. • The value of infiltrating the wound is unclear. • Antibody does not penetrate the blood-brain barrier.

30. Control of muscle spasms • Diazepam, a benzodiazepine and GABA agonist, is in wide use. • Barbiturates and chlorpromazine are considered second-line agents. • Mechanical ventilation and therapeutic paralysis with a neuromuscular blocking agent may be required for the treatment of spasms unresponsive to medication or spasms that threaten ventilation.

31. Prevention; immunization • 1-Passive immunization with TIG • 2-Active immunization with vaccine, preferably Td in persons over age 7

32. Prevention; active immunization • All partially immunized and unimmunized adults should receive vaccine, • The primary series for adults consists of three doses: • the first and second doses are given 4 to 8 weeks apart, • the third dose is given 6 to 12 months after the second. • A booster dose is required every 10 years • Combined tetanus and diphtheria toxoid (Td) adsorbed (for adult use), rather than single-antigen tetanus toxoid, is preferred for persons over 7 years of age.

33. For clean minor wounds • Td is administered to persons who have 1-unknown tetanus immunization histories 2-received fewer than three doses of adsorbed tetanus toxoid 3-received three or more doses of adsorbed vaccine, with the last dose given more than 10 years previously 4-Passive immunization with TIG is not recommended for clean minor wounds

34. Contaminated or severe wounds • Vaccine should be given to those; if more than 5 years have elapsed since the last dose. • It is given for all other wounds if the patient's vaccination history indicates unknown or partial immunization. • The dose of TIG for passive immunization is 250 U IM , which produces a protective antibody level in the serum for at least 4 to 6 weeks • Vaccine and tetanus antitoxin should be administered at separate sites in separate syringes.

35. Preventing neonatal tetanus • 1-Maternal vaccination even during pregnancy • 2-Efforts to increase the proportion of births that take place in the hospital

36. Prognosis • The application of methods to support respiration has markedly improved the prognosis in tetanus; mortality rates as low as 10 % have been reported • The outcome is poor; 1-in neonates and the elderly 2-in patients with a short incubation period, 3-a short interval from the onset of symptoms to admission, 4-or a short period from onset of symptoms to the first spasm (period of onset).