Tetanus is a non-communicable disease caused

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1 Proceediug S.Z.P.G.M.l. vol: 18(1): pp , Tetanus - Review of the Subject Farrukh Iqbal, Adnan Hussain Shahid Department of Medicine, Shaikh Zayed Postgraduate Medical Institute, Lahore SUMMARY Tetanus is a serious bacterial disease that leads to stiffness of your jaw muscles and other muscles. It can cause severe muscle spasms, make breathing difficult and, ultimately, threaten your life. A cut, puncture wound, laceration or other wound can lead to a tetanus infection and toxin production in someone without immunity. Spores of the tetanus bacteria, Clostridium tetani, usually are found in the soil but can occur virtually anywhere. If deposited in a wound, the bacteria can produce a toxin that interferes with the nerves controlling your muscles. Treatment is available, but the process is lengthy and not uniformly effective. Tetanus may be fatal despite treatment. The disease is rare in the Western world and developed countries due to proper vaccination programmes and a very small number of those result in death. However, in our setup he number of cases and resulting deaths is far higher. The best defense against tetanus is prevention by regular vaccination and making people aware of this potentially lethal but preventable disease.a review is presented here to highlight the problem. INTRODUCTION Tetanus is a non-communicable disease caused by a patent neurotoxin (tetano-spasmin) released by Clostridium tetani. The word tetanus comes straight from the Greek "tetanos" which means to stretch. Tetanus is still a common disease in the developing or under-developed countries and is one of the chief killing bacterial diseases. The disease is characterized by hypertonicity of muscles and spasms. Tetanus is a preventable disease and requires appropriate immunization for this purpose. Aetiology The causative agent is a gram pos1t1ve, strictly anaerobic, motile bacillus measuring µm wide and µm long. Spores develop terminally giving the organisms a characteristic drumstick-like appearance. The spores are survival structures which are resistant to d ry ing and disinfectants. The organism is ubiquitous and is found in soil. Clostridium tetani has also been isolated from operating theatre floor dust, operating tables, dressings, instruments cotton wool and even plaster on the walls 1 The vegetative cells are easily destroyed however the spores may survive for years and are resistant to boiling. Spores succumb to autoclaving 2 It can survive in dry sand and has been isolated from street dust 3. In human faeces it is usually absent but is found in faeces of cow, sheep, dog, guinae pig, rats and hens 4. Kerrin examined 300 samples without finding it but other workers have isolated it in a small percentage of samples more often from men in close contact with horses such as ostlers and grooms 4. In one instance, Cl. tetani was isolated from abdominal scar tissue of a woman who had tetanus l O years ago after removal of fibroids 5 Tulloch records the presence of Cl. tetani in the wounds of 19 soldiers who did not develop tetanus 6 Cl. tetani produces an exotoxin called tetanospasmin and ml of a potent filtrate is enough to kill a mouse. Tetanus toxin is destroyed by moist heat at 65 C in 5 minutes but in the dried state it can survive l 20 C for one hour. It is destroyed by the intestinal juices'. Another exotoxin, tetanolysin which is haemolytic toxin is also produced. but it is not involved in the disease otherwise. Tetanospasmin acts mainly at the CNS synapses. Epidemiology Tetanus is prevalent in Pakistan, India, Bangladesh, parts of South East Asia, Africa, the Eastern Mediterranean region and South America

2 F. Iqbal and A.H. Shahid 8 particularly that near equator. In developed countries like USA, UK and other European nations, the incidence is much less. In Britain, it is less than 40 cases I year. An average of 10 cases per year is reported in Australia. The case fatality rate is about I 0%. WHO estimated that about 715,000 deaths from neonatal tetanus occurred in 1990 and about 445,000 deaths were prevented by vaccination 9 Mortality rate has decreased even more with adequate intensive care; death to case ratio may be reduced to 10% to 20%. Highest risk of death is in the extreme of ages. There is substantial under reporting of the cases. The disease almost affects non-immunized or partially immunized subjects. Male sex is more vulnerable. The gardeners, farmers and those who deal with soil directly contract tetanus more frequently as compared to others 10 The disease occurs specially in rural areas, in warm climates and during summer probably reflecting increased exposure to contaminated soil or more frequent wounds. Acute injuries are the usual portals of entry of Cl. tetani. Tetanus follows injury, major or minor and sometimes the injury is too trivial and is overlooked. In a study of wounds incurred in the USA population the frequency of tetanus with portals of entry revealed the fol lowing 11 Table-I. neurotransmitters, including acetyl choline, peripheral, somatic and autonomic nerves Clinical manifestations The incubation period may vary from a day several months but more cases begin from 3 days 3 weeks but very long intervals are probably incubation period. In humans, toxin is absorord rapidly once it is produced. A short incubation less than a week usually leads to a sever attack ci longer incubation period are followed by m:"' attacks. The length of incubation period appare varies directly with the distance of the injury CNS. Injuries of lower limbs are associated wt long incubation period than injuries to head a:::d neck. However, there are two signs typical CJ tetanus - muscle rigidity and muscle spasm. The rigidity affects these groups of muscles i.c masseters, abdominal muscles and the erectors spine. For a day or two before the onset recognizable clinical signs, patient suffers fro=::. malaise, apprehension, sweating, sore throat or mi headaches but most commonly the first symptor= noticed is stiffness of the jaw. There are four clinical types of tetanus 14 Table I: Routes of tetanus infection. Portal Wounds Punctures Laceration Abrasions Crush Obstetric & Surgical Injections Ulcers (varicose - decubitus) Other wounds None found Frequency(%) Tetanospasmin is released only by proliferating Cl. tetani and release of this toxin in the CNS is complex. Tetanospasmin does not cross the blood-brain barrier, thus predominant means of transport appears to be neuronal, and causes its effect known as disinhibition. Freed from inhibition, exitatory reflexes lead to multiple tetanospasms. It also interferes with release of a variety of other Local tetanus It is the mildest disease where rigidity arc spasm is limited to the muscles near the infected wound and is confined close to the injury, and subsides spontaneously. It is mile and death to case ratio is less than I%. Generalized tetanus This is the commonest form of tetanus am:: accounts for about 80% of the cases. There is a prodrome consisting of malaise, headaches., restlessness, low grade fever, later trismus (lock jaw) occurs due to spasms of massete: muscles. Spasm of the facial muscles leads to risus sardonicus. This is followed by spasms of other somatic and visceral muscles of the body. Persistent and sustained spasm of the back muscles may give rise to opisthotonus.. The spasms are generalized, tonic muscule: contractions, often triggered by mild extema. stimuli e.g. sudden noise, drafts of cold air, - 46

3 Tetanus - Review of the Subject attempts to move or turn the patient. Internal stimuli e.g. distended bowel or bladder or mucous plugs in the airways may also trigger it. The classical tetanospasm consists of a sudden painful contraction of all muscle groups resulting in opisthotonus, abduction at shoulders, flexion of the elbows and wrists, and extension of the legs. Cognitive functions are not affected. Severe illness may be associated with temperature elevation to C. In severe cases, autonomic abnormalities may lead to hypertension, hypotension, flushing, diaphoresis, tachycardia and dysrrhythmias. The clinical course is highly variable. The illness is most intense during the first 1-2 weeks and then gradually subsides over the next 2-4 weeks. The disease may be mild with muscle rigidity and fewer spasms. Trismus, dysphagia, rigidity and spasms characterize moderately severe disease. Death occurs in % of cases depending on patient's age and care given. 3. Cephalic tetanus It is rare and generally associated with lesions of the head or face, especially in the distribution of the facial nerve and the orbit. Chronic otitis media has also been implicated. It is associated with atonic cranial nerve palsies involving III, IV, VII, IX, X and XII nerves singly or in combination. Trismus may be present. Disease has short incubation period i.e only 1-2 days and may progress to general tetanus and is invariably fatal. 4. Cerebral tetanus It is the name given to cases where, brain stem intoxication occurs due to toxin leading to hyperpyrexia, hypotension and thus leading to cardiovascular collapse. One should check pc0 2 or otherwise that ventilation is adequate because similar symptoms can occur due to this which can be correcte d eas1 'l y 15 Neonatal tetanus (Tetanus neonatorum) It is a form of generalized tetanus m newborns. It occurs in the neonates born to unimmunized or partially immunized mothers, commonly after non-sterile treatment of umbilical cord stump. It occurs during first two weeks of life and is usually severe The baby is normal at birth but after a few days have difficulty in suckling and excessive crying followed by variable degrees of trismus, dysphagia and then tetanospasms. In a study by Kurtoglu et al., 80.6% babies with tetanus had unhygienic home deliveries and few of the mothers of babies were immunized against tetanus 18 The death to case ratio in tetanus neonatorum is generally 60-80%. In a study from New York, protective levels of tetanus antitoxin have been detected in the cord sera of babies born to women who have been immunized earlier in life 19 COMPLICATIONS In mild cases complications are rare. Main danger arises from aspiration of secretions during spasms (Table 2). Table 2: Complications. System Complications Cardiovascular Hypertension, hypotension, tachycardia, bradycardia Neurological Cranial nerve palsies, brain stem damage, Metabolic Hypercatabolism, uremia, raised creatinine, weight loss, dehydration Renal Oliguria, acute tubular necrosis. acute renal failure Gastro-intestinal Haematemesis, gastric dilatation, paralytic ileus Pulmonary Aspiration pneumonia, rib fractures, pneumothorax, pulmonary embolism Miscellaneous Skin ulcers, septicaemia, muscle rupture, bone fractures, corneal ulcers, deep venous thrombosis, hyper-pyrexia, diaphoresis Aspiration pneumonia was found to be the commonest complication (37.2%). This was more common in patients who did not undergo tracheostomy (71.8%) as compared with those who underwent tracheostomy (28.2%). Second commonest complication was UTI (36.5%) 20. Sequelae There is no permanent organic sequelae after 47

4 F. Iqbal and A.H. Shahid tetanus unless bone fracture has occurred but some patients do suffer from temporary mental after effects. Others include irritability, sleep disturbances, fits myoclonus, postural hypotension, and loss of libido 21 Overall mortality in Pakistan is 40.6% a reported by Raza et al 22 In another study from Mayo hospital Lahore, one of the largest unit for tetanus, it was concluded that majority of complications are preventable. The main complications included aspiration pneumonia and UTI leading to septicaemia 20 Fever is secondary to infections rather than muscular over activity 23 DIAGNOSIS The diagnosis is based primarily on clinical manifestations and secondarily on epidemiologic history. The typical trismus, risus sardonicus and spasms are diagnostic. There is hypertonicity with exaggerated deep tendon reflexes and absence of sensory involvement. History of wound and absence of immunization is also supportive. A patient with a history of full immunization should be considered to have tetanus only after thorough exploration of alternative diagnoses. Laboratory investigations are usually noncontributory. Moderate leukocytosis is common. CSF is normal but its pressure may be raised probably due to muscle spasms 2 Cultures of contaminated wounds are usually negative. Electroencephalography (EEG) or electromyography (EMG) are not helpful. Low or undetectable concentrations of antitoxin in serum collected at the time the patient is examined are compatible but not diagnostic of tetanus 24 Other tests which are more specific and sensitive consist of passive haemagglutination enzyme immunoassay, radio-immunoassay, immuno-fluorescent assay, latex agglutination and a variety of methods using agar gel precipitation. DIFFERENTIAL DIAGNOSIS Tetanus should be differentiated from many other neurological and non neurological disorders and it depends on the clinical pattern of tetanus. When trismus is present alone, it should be differentiated from other causes of difficulty in opening the mouth e.g. dental caries, tonsillitis, peritonsillar abscess and temporomandibular joint (TMJ) dysfunction ( especially after serum sickness when prophylactic antitoxin is given). Bacterial meningitis, encephalitis or meningo-encephalitis may be accompanied by trismus and muscle spasms but the history of onset and mental state are different and CSF is abnormal too. Status epilepticus with its marked mental changes could only deceive the very in experienced. Hypocalcaemic tetany may result in muscle spasm and opisthotonic posturing but not associated with trismus and it affects mainly the distal parts of the limbs, not the trunk and is confirmed by finding low serum calcium. Rabies may cause muscle spasms, particularly in the muscles of respiration and deglutition. However it is more likely to be associated with hallucinations, hydrophobia, mania and stupor. Seizures in rabies are likely to be clonic in contrast to tonic seizures of tetanus. Poliomyelitis in a rare form may present like tetanus in which trismus is also present. Strychnine poisoning mimics general tetanus, however, trismus usually appears late and is not persistent, body temperature is normal and symptoms and signs usually develop much more rapidly than with tetanus. Muscle rigidity during spasm is usually absent with strychnine poisoning and a history suggesting poisoning may be obtained, and the diagnosis can be confirmed by finding strychnine in the gastric contents or urine. Pain in abdomen, associated with rigidity in the preconvulsive stage may suggest an abdominal lesion and more than one patient with tetanus have mistakenly been operated on. The presence of trismus and arching of back should help to diagnose tetanus. Phenothiazine reactions may cause trismus but are frequently associated with tremors, athetoid movements and torticollis. Detection of phenothiazine in the urine or amelioration of symptoms with diphenhydramine or procyclidine confirms diagnosis. Hysterical conversion reactions may also mimic tetanus but these patients are more likely to relax with prolonged observation or when distracted. The history may reveal underlying hysterical personality disorder. Other conditions to consider may be subarachnoid haemorrhage and alcohol withdrawal in the differential diagnosis of tetanus. 48

5 Tetanus - Review of the Subject TREATMENT Tetanus is self-limiting disease. Jf patients could be kept alive by therapeutic measure for 3 weeks, they would probably all make a complete recovery. Management Protocol for general tetanus* Diagnosis and stabilization: First!tour A. Assess airways and ventilation and.if necessary, prepare for endotracheal intubation under benzodiazepine sedation and neuromuscular blockade (e.g vecuronium mg/kg). B. Obtain samples for antitoxin level, strychnine and dopamine antagonist assays, electrolytes, blood urea nitrogen, creatine kinase and urinary myoglobin determination. C. Determine the portal of entry, incubation period, period of onset and immunization history. D. Administer benztropine (1-2 mg IV) or diphenhydramine (50 mg IV) to prevent a dystonic reaction. E. Administer a benzodiazepine IV (diazepam in 5-mg increaments,or lorazepam in 2-mg increments) to control spasm and decrease rigidity. Initially, use a dose adequate to produce sedation and mm1m1ze reflex spasms. If this dose compromises the airway or ventilation, intubate using a short acting neuromuscular blocking agent before transferring the patient to a quiet, darkened area of the ICU. Early management phase: First 24 hours A. Administer human tetaus immunoglobulin (TIG), U IM. Consider giving part of the TIG IM in the area of the implicated wound (if any) B. At a different site, give adsorbed diphtheria) and tetanus toxoid (0.5 ml) or diphtheriatetanus-pertussis vaccine (0.5 ml),as appropriate for age, IM. Adsorbed tetanus toxoid is available for patients with a history c. D. E. F. G. of reaction to diphtheria! toxoid; otherwise, the correct combination for the patient's age should be used. Begin IV metronidazole (loading dose of 15 mg/kg infused over I hr, followed by maintenance doses of 7.5 mg/kg infused over I hr period every 6-8 hr ie mglkgld, not to exceed 4g/24hr for 7-14 days. As regards other antibiotics, Cl. tetani is usually sensitive to penicillin, metronidazole, cephalo sporins, imipenem, macrolides and tetracyclines. In a comparative trial, metronidazole gave better results than penicillin. Theoretically, penicillin, a centrally acting GABA antagonist may act synergistically with tetanospasmin. Penicillin G mg (about 100,000U)/ kg/day, IV four hourly for IO days should kill vegetative forms of Cl tetani, However if there is a large amount of ischaemic tissue, larger doses ( mg i.e U) I kg/day IV 4 hourly) may augment diffusion into tissues. Patients who are allergic to penicillin and cannot be treated with metronidazole may be treated with tetracyclines 30 mg per kg/day IV 6 hourly. Perform a tracheostomy after placement of an endotracheal tube and under neuromuscular blockade if spasms produce any degree of airway compromise. Debride wound if indicated. Place a soft, small-bore nasal feeding tube or a central venous hyperalimentation catheter. Give benzodiazepines as needed to control spasms and produce sedation. If adequate control is not achieved, initiate long-term neuromuscular blockade with vecuronium; continue benzodiazepines for sedation with intermittent EEG monitoring to ensure somnolence. Intermediate management phase: Next 2-3 weeks A. Treat sympathetic hyperactivity with labetalol ( mg/min) or morphine ( mg/kg/h). Consider epidural blockade with 49

6 F. Iqbal and A.H. Shahid local anesthetics. Do not use diuretics for blood pressure control because volume depletion will worsen autonomic instability. B. If hypotension is present, place a pulmonary artery catheter and an arterial line and give fluids, dopamine, or norepinephrine. C. Sustained bradycardia usually requires a pacemaker. Atropine or isoproterenol may be useful during pacemaker placement. D. Begin prophylactic heparin. E. Use a floatation bed if possible to prevent skin breakdown and peroneal nerve palsies. Otherwise ensure frequent turning and use antirotation boots. F. Maintain administration of benzodiazepines until neuromuscular blockade. Taper the dose over days. G. Begin rehabilitation planning. Convalescent stage: 2-6 weeks A. When spasms are no longer present, begin physical therapy. Many patients require supportive psychotherapy B. Before discharge, give another dose of tetanus -<liphtherial or diphtherial-tetanuspertussis vaccine. C. Schedule a third dose of toxoid to be given 4 weeks after the second. SPECIFIC TREATMENT For a suspected case the wound should be debrided. In some centers local infiltration of 3000 units of antitoxin around the wound is advocated. This should be given prior to debridement. Injection of human tetanus antitoxin 250 units and tetanus toxoid at different sites is given. If the immunization status is not known, the full three-dose course of vaccine is given. Lastly, the patients who recover should be actively immunized because proper immunity is not achieved after the disease process. The other aspects of management include wound management, antibiotics and antitoxin. IMMUNIZATION Antitoxin lowers mortality but only if the toxin is not fixed to the nerve cells. It only nurtralizes the toxin still being produced and absorbed. If toxin is circulating in blood stream, antitoxin will destroy it. On the other hand patients treated with antitoxin, protective levels of anti toxin have been found in the blood during 7 to 14 days of illness, yet have not prevented the death 2 5 Pyridoxin may counteract the effects of toxin at the level of synapse. It was tried with doubtful success in two series of neonatal cases 26.A dose of l 0,000 units is as good as if not better than 120,000 units 2 7 Either equine or human antitoxin can be given. The former is given in doses of l 0,000 units toxin after test dose. It is cheaper than human but carries risk of fatal anaphylaxis. Generally the patients should receive u injected IM in several sites. Infiltration of part of the dose around the wound may neutralize the toxin at the site of production. Antitoxin is absorbed regularly and concentration in the serum peaks aboot hrs after administration. Exogenous antitoxin does not cross the blood brain barrier and has no effect on toxin already fixed to nervous tissues. Randomised controlled trials have not consistently revealed benefit from intrathecal anti-toxin and the tetanus immunoglobulins (TIG) available in the USA is not licensed for intrathecal use, hence this route of administration is not recommended Intrathecal TIG has been recommended by Sherrington as long ago as In one controlled trial in 1979 in infants there was no difference in duration of illness or mortality between groups given or not given intrathecal TIG Recovery from tetanus frequently does not result in immunity against further attack, all patients should be immunized with tetanal toxoid either at the time or diagnosis or during convalescence. TIG does not interfere with active immunization and active immunization does not interfere with the therapeutic effects oftig. PREVENTION It is well said that prevention is better than cure and this is achieved by immunization. The 50

7 Tetanus - Review of the Subject most effective is active immunization with tetanus toxoid. The other is injection of anti toxin as soon after the injury as possible in the hope of destroying toxin before it enters the nerve cells. The most trivial and innocent looking wound may harbour toxin producing bacilli, yet undetected till the signs of clinical tetanus appear. Prevention of tetanus in the community should include vaccination of pregnant women, infants, children and adults. Anti tetanus toxoid should also be given before emergency surgery, deliveries and obstetric procedures. In a study it was found that none ( 0% ) out of total 180 had complete immunization. 8.8% had partial immunization out of which 3.3% had single dose of toxoid and 5.5% received single Injection of A TS, whereas 92.8% had no immunization 31 Maternal antitoxin crosses the placenta and protective levels are found in the cord sera of babies born to immunized women 3 2 Aseptic treatment of umbilical cord stump is very important in preventing neonatal tetanus. Topical application of antimicrobials to the cord particularly in developing countries is a new preventive modality; however this is not the alternative of maternal vaccination and hygienic delivery 33. Active Immunization Tetanus toxoid is one of the most effective immunizing agents available since A primary series is virtually I 00% effective for 5 (and probably 10) years after the last dose. Routine immunization should begin at 6 to 12 weeks after birth with diphtheria and tetanus toxoid combined with whole cell pertussis vaccine (DPT). See table 3. The recommendations for primary immunization with tetanus toxoids are shown in Table 3. Tetanus neonatorum can be prevented by making sure that pregnant women are immune to tetanus so that they will pass sufficient antitoxin trans-placentally to protect the newborn. Two doses of tetanus toxoid (Td) given at least 4 weeks apart to a pregnant woman, with the last dose at least 2 -eeks before delivery will reduce morbidity and rtality from neonatal tetanus. Trained midwives.h aseptic techniques have substantial impact in nting tetanus. Other wise following plan should be observed and adopted (Table 4). Table 3: * + t $ & # Recommendations for primary immunization with tetanal toxoid by age at beginning of immunization. Vaccine <l yr Age f rou {1-6 r s} '::_1 yr Interval DTP "' OR DTP & DT + Td# Before DT+.t Dose I First visit I'' visit I'' visit First visit Dose mo 1-2 mo 1-2 mo 1-2 mo Dose3 1-2 mo 1-2 mo 6-12 mo 1-12 mo Dose4 -I yr I yr Table 4: DTP, diphtheria! and tetanal toxoids and pertussis vaccine; DT, diphtheria! and tetanal toxoids for pediatric use; Td, tetanal and diphtheria! toxoids for adult use OT for those with contraindications to pertussis vaccine Booster with OT or DTP (dose 5) indicated at 4-6 yr of age. Boosters with Td indiated every IO yr thereafter. First visit generally at age 2 months. Dose 5 of DTP indicated at 4-6 yr of age unless dose 4 was given at '::._ 4 yr of age; in this instance, dose 5 not needed. Boosters with Td indicated every 10 yr after dose 4 or 5. Diphtheria] and tetanal toxoids and acellular pertussis vaccine (DTtaP) preferred for doses 4 and 5. Dose 4 of DT indicated at 4-6 yr of age unless dose 3 was given at '::._ 4 yr of age; in this instance, dose 4 not needed. Boosters with T d indicated every IO yr after dose 3 or 4. Boosters with Td indicated every IO yr. History of adsorbed tetanus toxoid Guide to tetanus prophylaxis and wound management (modified from an MMWR Morb Mortal Wkly Rep 1991; 4: 70. Unknown or < 3 doses 3 or more doses Clean minor wounds 1 Td 2 TIG 3 Yes No 4 No No All other wounds Td 2 TIG 3 Yes No 5 Yes No I. Such as but not limited to wounds contaminated with dirt, faeces, soil, saliva etc. puncture wounds, avulsions, and wounds resulting forum missiles, crushing, bums and post bite Tetanus toxoid and diphtheria toxoid adult form. Use only this preparation (Td adult) in children older than 6 years. Tetanus immune globulin Yes, if more than 10 years have elapsed since last dose. Yes, if more than 5 years have elapsed since last dose (more frequent boosters are not needed and can enhance side effects). 51

8 F. Iqbal and A.H. Shahid So far single dose vaccines have been tried with some success but there is yet no vaccine which is completely reliable It was found that 80% of 410 Indian who had never been immunized against tetanus nevertheless had measurable antitoxin in their serum, presumably from chronic clostridial contamination of the intestines 36. In developing countries it is difficult to organize a three dose immunization programme; therefore it can have a great advantage. Too frequent injections of toxoid must be avoided as they produce excessively high titres of antitoxin in the blood and may lead to increased reaction to toxoid In a study from Haryana India, coverage for tetanus immunization was 44.3% among 17 year old girls and 26.7% among 11 year old girls. The coverage was better (35%) among school going girls as compared to non-school going girls ( 13% ) 4. WHO SHOULD RECEIVE THE VACCINE? I. Adults especially those 50 years and older because most of the tetanus cases in recent years have occurred in this age group. 2. Persons who are not sure whether they have received the initial series of tetanus shots or boosters. 3. Travelers, especially to countries with hot, damp climates and soil rich in organic matter Agricultural workers and other who work with dirt or manure. Persons whose job or recreational activities expose them to cuts and scrapes. Those who are recovering from tetanus, because suffering from tetanus does not confer lasting immunity as is true for some other diseases. Injured persons who may require emergency tetanus treatment depending on their immunization status (primary immunization, boosters) and the type of wound received. Pregnant women who have not been immunized or may be inadequately immunized or who may deliver their infants tn unhygienic circumstances. After immunization, antibodies are passed from the mother to the fetus through the placenta. WHO SHOULD NOT RECEIVE THE VACCINE? 1. Children with moderate to severe fever can be vaccinated as soon as they have recovered. 2. Persons on immunosuppressive therapy given for cancers or other treatments may not develop the same immune response as a normal person. It is important to defer the immunization for one month. 3. Any person who experiences difficulty in breathing following a previous dose of tetanus toxoid (Td). Skin testing is important before doing this. 4. Persons who develop encephalitis with in 7 days of DTP should not receive additional immunization containing pertussis vaccine. 5. Family history of convulsions or other central nervous system disorders does not justify with holding DTP immunization. Tetanus toxoid may induce IgE antibody formation, but allergic reactions are rarely reported i.e., 1/100,000 injections. Passive immunization A dose of 1500 units of equine tetanus antitoxin (A TS) given to an adult will maintain a titre of 0.2 units antitoxin per ml in his serum for about 2 weeks. Antitoxin must be given as soon as possible after injury as otherwise toxin may already have reached the central nervous system. If such a patient is given antitoxin, it is eliminated rapidly from circulation by these precipitins and rendered useless 40 Therefore when a patient is given horse serum for any reason, he should be actually immunized thereafter by toxoid against tetanus. PROGNOSIS The prognosis is influenced by various factors including age, immunization status, underlying illness, degree of illness and quality of 52

9 Tetanus - Review of the Subject supportive care. Most vital is the critical or intensive care. In the past, death to case ratio for general tetanus exceeded 40%, however with intensive care ratios of only 10% to 20% may be attained. The highest death to case ratio is at extremes of age group i.e. very young and very old. Patients who had one or no prior doses of tetanus toxoid are also at higher risk. In the past, it was thought that if the incubation period is less than 7 days the outcome is fatal and if more than 7 days the outcome is better but according to recent experience, it is not true. Local tetanus has the best prognosis, and general or cephalic tetanus has worst prognosis. Paroxysmal spasms, whether present on admission or later are associated with substantially greater mortality. In general, the more rapid the evolution of symptoms and signs, the worst is the prognosis. The main cause of death from tetanus is from asphyxiation during a muscular spasm, cardiovascular complications or a secondary infection such as bacterial pneumonia or bacteraemia. Patients who survive the acute phase without residual deficit usually recover completely. Clinical tetanus usually does not induce immunity against secondary attacks of the disease because the minute amount of circulating tetanus toxin may be insufficient to induce or increase immune response. FUTURE The greatest problem in tetanus is not case management; it is the failure to deliver highly effective immunization i.e tetanus toxoid to the population in need. Particular attention should be paid to the wound management. More than 3 quarters of cases of tetanus reported in the USA between 1972 and 1989 had acute injuries. Of these, at least I /3 sought medical care for their wounds. Of 285 patients reported to have undergone wound debridement, 93% did not receive Td or TIG as was indicated. Similarly neonatal tetanus, the second most common cause of vaccine-preventable deaths in the world (after measles) could be eliminated by universal immunization of women of child bearing age. More research is required to develop a toxoid that would successfully immunize women of childbearing age with a single dose. The smaller the number of doses, the greater the probability of success of programs in developing countries. This type of vaccine should give a longterm immunity throughout the years of reproduction to induce long term protection. Currently these approaches include micro encapsulation of tetanus toxoid, use of live bacterial vaccine to express a nontoxic fragment of tetanus toxin, and adjuvants to enhance the immunogenicity of tetanus toxoid. Micro encapsulation with bio degradable polymers that release tetanus toxoid in a controlled manner may be an ideal delivery system for a new tetanus vaccine. Single injection may replace the three - dose primary series and eliminate the need for subsequent booster doses. Another breakthrough is construction of a genetically defined salmonella typhi Ty 2 aro A, aro C mutants as a candidate per oral typhoid I tetanus vaccine. This mutant strain of S, typhi expresses a non toxic 50-kd fragment of tetanus toxin (fragment-c) from a gene incorporated into the chromosome. In experimental studies, the vaccine protected mice against a lethal challenge of tetanus toxoid. Finally immunoadjuvants such as liposomes may increase the immunogenicity of tetanus tox.oid thus need for multiple doses of tetanus toxoid would be decreased. Sero-surveys in the USA during late 1970s and 1980s showed that about 10% of persons of age and 50% to 65% of those over 60 years of age lack protective levels of circulating tetanus antitoxin and are presumably susceptible. All adults should have completed their primary vaccination at some part of their lives and should have boosters after every 10 years to maintain a level of immunity. Therefore it is utmost important to identify those in need of primary series or boosters doses and to ensure that they receive the needed protection. Health care providers must use every opportunity to review vaccination histories and give tetanus toxoid preferably with diphtherial toxoid to patients with unknown or inadequate history, especially to older adults, who are the most susceptible group and have the highest risk of death from tetanus 41. Tetanus is a preventable disease therefore, good old slogan stands true "prevention is better than cure" in this disease which has very light morbidity and mortality. 53

10 F. Iqbal and A.H. Shahid REFERENCES I. Robinson DT, McLeod.TW, Downie AW. Dust in surgical theatres as possible source of postoperative tetanus. Lancet 1946; I: 152. Hoeprich PD, Jordan MC, Ronald AR. Tetanus infection diseases - A treatise of infectious processes Edition, J.B. Lippincott Company, Philadelphia, 1994; Gillies EC. Isolation of tetanus bacilli from street dust. J Am Med Assoc, 1937; 109: Tapley WWC, Wilson GS. Principles and practice of bacteriology and immunity Arnold, London. 5. Bonney V, Box C, MacLennan J. Tetanus bacilli recovered from the scar ten years after an attack of post operative tetanus. Br Med J 1938; 2: Tulloch WJ. J Hyg Camb 1919; 18: 103 quoted by Topley and Wilson. 7. Weatherall DJ, Ledingham JGG, Warrell DA, Tetanus ( ) Oxford Text Book of Medicine Vol I, 3 rd Ed, Oxford Medical Publications. New York 1996: Gassee F. Global and regional estimates of neonatal tetanus death Geneva, Switzerland World Health Organization (WHO), 1991 (Doo /WHO/RD/91/WP 9 AP) 9. Report Tetanus Surveillance England and Wales: CDR 84/87 Publ. Hlth Lab Serv, London. I 0. Handerson SO, Mody T, Groth DE, Moore JJ, Newton_ E. The presentation of tetanus in an emergency department. J Emerg Med. 1998; 16: Bleck TP. Tetanus, In Scheid WM, Whittley RJ, Durack DT (eds). Infections of the central nervous system. New York: Raven Press, 1991, Black TP. Tetanus: Pathophysiology, management and prophylaxis. Dis Mon 1991; 37: Edmonson RS. Tetanus. Br. J Hosp Med, 1980; Rowland LP. Infections of the Nervous System, Merritt's Text Book of Neurology Ninth Ed, William &Wilkins; 1995: Smythe PM. Studies on neonatal tetanus and pulmonary compliance of the totally relaxed infants. Br Med J 1963; l: Nkrumah FK, Verma A. Neonatal Tetanus. Analysis of 161 cases from Accra Ghana. Med J 1971; 10: Handalage DCM, Wickramasinghe SVDC. Neonatal Tetanus - some observations from SriLanka, J Trop Pediatr Environ Child Hlth 1976; 22: Kurtoglu S, Caksen H, Ozturk A, Cetin N, Poyrazoglu H. A review of 207 newborns with tetanus. JPMA, 1998; 48: Nathenson G, Zakzewski B. Current status of passive immunity to diphtheria and tetanus in the new born. J Infect Dis 1976; 133: Hussain I, Afzal N, Nadeem A, Sheikh SS, Shah AA. Complications of tetanus in adult patients in Pakistan. The professional Medical Journal 1998; 5; Illis LS, Taylor FM. Neurological and electro-encephalographic sequelae of tetanus. Lancet 1971; l: Raza SN, Hussain I, Amjad M, Shah AA. Prognostic factors in adult tetanus. J Postgrad Med Ins 1997, 8(3, 4): Udwadia EF Lall A, Udwadia ZF, Slkhar M and Vora. Tetanus and its complications, intensive care and management experience in 150 Indian patients. Epidemiol Infect 1987; 99: Repetti CF, Gill TJ. Radioimmunoassay of lg G anti tetanus toxoid antibody. J Immunol Methods 1980; 37: Patel JC, Mehta BC, Nanavali BH, Hazra AK, Rao SS, Swaminathan CS. Role of serum therapy in tetanus. Lancet! 963; I: Godel JC. Trial of pyridoxin therapy for tetanus neonatorum. J Infect Dis 1982; 145: Patel JC, Aujar AA, Mehta BC, Nanavali BH. Dosage of antitoxin serum in the treatment of tetanus. Indian J Med Sci. 1960; I 0: Sherrington SC. Observation with anti tetanus serum in the monkey. Lancet 1971; 2: Onuora CA, Sambo-Donga L, Yahya H. Intrathecal antitetanus serum in the management of tetanus. E. Afr Med J 1982; 54

11 Tetanus - Review of the Subject Neequaye J, Nkeumals FK. Failure of intrathecal antitetanus serum to improve survival in neonatal tetanus. Arch Dis Childh 1983; 58(4): Mehboob F; Immunization status in cases suffering from tetanus. Pakistan J Med Sci. 1998; 14: Christie AB. Tetanus, Infections diseases; Epidemiology and clinical practice; vol 2; 4th Ed, Churchill Livingstone: 1987; Parashar UD, Benett N, Boring JR, Hlady WG. Topical antimicrobial applied to the umbilical cord stump, a new intervention against neonatal tetanus. Int J Epidemiol 1998; 27: White WG, Gall D, Barnes GM, Barker E, Griffith AH, Smith JWG. Duration of immunity after active immunization against tetanus. Lancet 1969; 2: Veroneri R, Correa A, Alterio D. Single dose immunization against tetanus. Promising results in human trials. Revta Inst Med Trap S Paulo 1970; 12: Dastur FD, Awatramani VC, Dixit SK, Dsa JD, Cooverji ND, Suni A. Response to single dose of tetanus vaccine in subjects with naturally acquired tetanus antitoxin. Lancet 1981; 2; Edsall G, Elliott MW, Peebles TC, Levine L, Eldred MC. Excessive use of tetanus toxoid boosters. J Am Med Assoc 1967, 202: Peebles TC, Levine L, Eldned MC, Edsall G. Tetanus toxoid emergency boosters. A reappraisal. N Engl J Med : StanField JP, Gall D, Bracken PM. Single dose antenatal tetanus immunization Lancet 1973; 1: Woodward WW. Tetanus ten days after administration of anti tetanus serum. Br Med J. 1960; 2: Simonsen 0. Vaccination against tetanus and diphtheria. Evaluation of immunity in the Danish population guidelines for revaccination and method for control of vaccination programme. Dan Med Bull 1989; 36: The Authors: Farrukh Iqbal Associate Professor Department of Medicine Shaikh Zayed Postgraduate Medical Institute Lahore Adnan Hussain Shahid Trainee Registrar Department of Medicine Shaikh Zayed Postgraduate Medical Institute Lahore Address for correspondence: Farrukh Iqbal Associate Professor Department of Medicine Shaikh Zayed Postgraduate Medical Institute Lahore figbal56@hotmail.com 55

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