TETANUS

Tetanus is an acute life-threatening illness, characterized by painful muscular spasms and stiffness continues to be a significant cause of morbidity and mortality in children despite the availability of a safe and high effective vaccine for many decades.

However, Tetanus neonatorum, the severest form of tetanus in newborns has been eliminated from India since 15^th May 2015.

Epidemiology: C. tetani is gram-positive anaerobe, present as spores in stools of various herbivores animals. These spores survive for many years in fecal-contaminated soil and cannot be killed by boiling, but easily by autoclave.

Tetanus spores from soil enter the body via: (a) contaminated wounds, usually a penetrating or crush injury, (b) perforated ear canal in otitis media (otogenic tetanus), (c) unsterilized needles/surgical instruments, and animal bites. Neonatal infection due to cord-cutting by unsterile blade/scissors is now extremely rare.

Pathogenesis: At the site of entry, the spores germinate, proliferate and produce a powerful exotoxin, i.e. tetano­spasmin. Being strongly neurotropic, this toxin binds at neuromuscular junction and traverses along the axonal sheaths towards the spinal cord. In cord, it blocks the release of neurotransmitters in inhibitory spinal interneurons, leading to simultaneous agonist-antagonist muscular action, i.e. typical muscular spasms. The role of Tetanolysin - another exotoxin released in tetanus is unclear, perhaps contributing to produce anaerobic environment by damaging surrounding tissues.

Clinical manifestations range from localized or provoked trismus to generalized, severe, frequent and spontaneous muscle spasms. A typical case presents after incubation period of 5-15 days with three overlapping stages, as follows:

a. Stage of trismus (lock-jaw) is characterized by painful spasm of masseters with difficulty in opening the mouth, chewing and swallowing.

b. Latent period is the time-lag between onset of trismus and appearance of spasms, usually not more than 2-3 days. Duration of latent period is inversely related to the severity of disease.

c. Stage of spasms is characterized by: (i) reflex spasms—sudden, painful tetanic contractions of voluntary muscles with hyperextension of limbs and back on slightest provocation, e.g. sound, touch, light or even wind movements, (ii) spontaneous or unprovoked spasms in severe disease, and (iii) laryngeal spasms—commonest cause of death in these children. Moderate fever and signs of autonomic imbalance, e.g. tachycardia and hypertension, are present in some cases.

As a rule, the sensorium remains normal even in severe or terminal cases of tetanus, unless clouded by hypoxia due to respiratory failure or other co-existing disease.

Other presentations include:

• Localized tetanus—the mildest form with painful muscular rigidity and spasm around the site of injury,

e. g. trismus in otogenic tetanus.

• Cephalic tetanus—the rarest variant, with cranial nerve palsies, trismus, risus sardonicus, lid-retraction and spastic paralysis of tongue and pharynx, but without generalized muscular rigidity.

• Neonatal tetanus usually presented from 3^rd 14^th day, with refusal to accept breastfeeds, gradually progressing to full-blown picture over few hours.

Complications result from: (a) mechanical injury due to violent muscle spasms, (b) airway obstruction due to laryngeal spasms, (c) autonomic disturbances, and (d) therapeutic procedures (Table 10.26).

Diagnosis is mainly clinical, based on: (i) history of injury or otitis media, (ii) unimmunized status, and (iii) typical clinical features, e.g.

Spatula test, i.e. clenching of teeth on insertion of a spatula into the patient's mouth, is useful to demonstrate mild trismus in doubtful cases, though should be avoided in an obvious case due to risk of oral mucosal injury.

While rarely required, diagnosis may be confirmed on wound cultures for C. tetani, positive in lt;40% cases.

Investigations are also indicated to: (a) identify concomitant infection at the site of entry, e.g. wound/ ear-swab cultures, (b) detect serious complications and (c) exclude other causes of muscle spasms.

D/D includes: (a) rabies (history of dog bite, hydrophobia),

(b) strychnine poisoning (extremely rare), (c) meningitis (abnormal sensorium/CSF), (d) tetany (carpopedal spasms), (e) phenothiazine dyskinesia (history of drug exposure, transient course) and (f) pseudotrismus due to painful conditions, e.g. dental or parapharyngeal abscess. Treatment of tetanus aims to: (a) neutralize circulating exotoxin by antitoxin, (b) prevent further toxin production by local wound care and antibiotic therapy,

(c) prevent muscular spasms, and (d) treatment of complications.

All cases need to be hospitalized irrespective of severity. Important steps in management are:

a. Nursing environment: The child should be nursed in a dark-quite room with minimum stimulation, as even slight light/sound may stimulate painful spasms.

b. Wound care with cleaning and debridement of dead tissue to prevent anaerobic conditions that favour clostridial growth. Though cultures are usually negative for clostridia, wound/aural cultures should be collected to identify secondary infections.

Fig. 10.7: Tetanus: (A) Trismus; (B) Ophisthotonus.

TABLE 10.26: Complications of tetanus

Mechanical injuries:

• Tongue or lip injuries

• Compression fractures bones, e.g. spine

• Muscle fractures and/or rhabdomyolysis

Airway obstruction due to laryngeal spasms

• Sudden choking and death

• Aspiration pneumonia

Autonomic disturbances

• CVS: Hypertension/hypotension, arrhythmia

• GIT: Paralytic ileus, acute gastric dilatation

Iatrogenic complications

• Over-sedation: Apnea or respiratory failure

• Nursing-related: Bed-sores, aspiration

c.

d. Antibiotics to arrest further growth of clostridia and production of antitoxin, as well as to prevent secondary infections. Metronidazole (IV 30 mg/ kg/d q6hr) is the preferred choice than conventional penicillin, which is a GABA-antagonist like tetanus toxin and can accentuate spasms.

e. Active immunization with a single dose of TT/Td (0.5 ml deep IM) is indicated in all cases on admission to initiate active antibody formation, irrespective of previous immunization status.

f. Sedation is cornerstone of symptomatic therapy in tetanus, to prevent and control the spasms. Level of sedation has to be adjusted according to severity of disease. Mild cases without spasms may be treated with single drug, i.e. diazepam, given orally via intra- gastric tube or per-rectally. However, severe cases require either high-dose monotherapy (oral or IV diazepam) or multi-drug sedation (additional drugs,

e. g. phenobarbitone and/or chlorpromazine).

A general practice is to start with a single drug-diazepam IV (0.1-0.2 mg/kg every 3-6 hr) and gradually increase the dose, till spasms are controlled or safe-limit is reached. In controlled cases, IV therapy may be substituted with oral preparation via intragastric tube. In uncontrolled cases, additional drugs may be added gradually in increasing doses. Some basic rules of sedation therapy are:

- Parenteral sedation is risky than oral therapy and should be used only for initial control or in severe cases.

- Drug-doses should be increased gradually, but never to exceed safe-limits.

- IV bolus of sedatives should be given very slowly, to avoid sudden respiratory depression.

- When multiple drugs are used, simultaneous administration should be avoided.

- Sedation is gradually tapered after the patient is spasm-free for minimum seven days.

- Occasional breakthrough spasms in a controlled case are not uncommon, which may be treated with additional doses of IV diazepam (0.2-0.5 mg/kg).

IV magnesium sulphate has been used as an adjunctive drug to reduce the doses of benzo­diazepines with added benefit of controlling autonomic symptoms. Magnesium is a pre-synaptic neuromuscular blocker, which blocks the release of catecholamines from nerves and reduces receptor responsiveness to released catecholamines. Hypotension and respiratory depression are major adverse effects of magnesium therapy.

g. Muscle relaxants, e.g. pancuronium or anesthesia with ventilatory support may be required in refractory cases to maximize sedation. Other muscle relaxants, e.g. baclofen, if required, should also be used only in intensive care settings.

h. Supportive care includes: (i) Adequate nutrition via nasogastric tube or IV, (ii) airway maintenance with frequent suction and/or tracheostomy, (iii) breathing support with oxygen/assisted ventilation, (iv) back, bowel and bladder care and (v) management of complications. Percutaneous gastrostomy may be used for feeding to minimize the risk of aspiration.

Outcome: Overall mortality is post-neonatal tetanus is 15-20%, usually due to laryngospasm or aspiration.

Outcome is poor in—(a) younger children, (b) shorter incubation period (lt;7 days), (c) shorter latent period (lt;48 hours), (d) higher frequency and duration of spasms, (e) presence of autonomic disturbances, (f) concomitant complications, e.g. aspiration and airway obstruction and (g) quality of nursing care and sedative therapy. Patel and Jog criteria may be used to assess the severity of tetanus (Table 10.27).

In survivors, long-term sequelae, e.g. cerebral palsy, mental retardation and behavioral problems, are not uncommon due to hypoxic brain damage during spasms.

• Active immunization with three doses of primary immunization at 6, 10 and 14 weeks and boosters at 18 months and 5 years (DTwP or DTaP), followed by Td at 10 years of age and subsequently at every 10 years (TT). IAP recommends a single dose of Tdap at or after 7 years of age, followed by Td every 10 years (Ch 9.2.1). Antenatal immunization of mothers with two doses of Td at 4 weeks interval, starting in early

pregnancy (single dose in subsequent pregnancies) is vital to prevent neonatal tetanus.

• Prevention of spore-entry by immediate wound care, treatment of otitis media, trained obstetrical care, etc. Safe delivery practices include cord-cutting by sterile blade with no subsequent contaminated dressings.

• Passive prophylaxis with tetanus immunoglobulin (TIG) is indicated in: (a) potentially infected severe wounds with incomplete or unknown previous immunization status, (IM 5000 IU) within 3 days of injury, and (b) babies born to unimmunized mothers (IV 250-500 IU), within 6 hours of birth. Anti-tetanus serum of equine origin (ATS) is no longer recommended due to serious side effects.

• Post-injury TT immunization schedule depends on previous immunization status (Table 10.28); using any age-appropriate tetanus containing vaccine (DPT/ Tdap/Td/TT).

Other important clostridial infections in children are as follows:

Pseudomembranous colitis (PMC): It is an acute dys­entery-like illness, due to overgrowth of pathogenic C. difficile or C. perfringes in gut.

Pathogenesis: Preceding antibiotics therapy (specially ampicillin) is most important risk factor for PMC, which damages normal gut flora to facilitate clostridial growth. Pathogenicity of these strains is mediated by production of two toxins—toxin A (enterotoxic) and B (cytotoxic).

Clinically, most cases present with mild self-limiting diarrhea, but a typical case presents with bloody dysentery and passage of pseudomembranes (mucosal sloughs) in stools. Constitutional features, e.g. fever, abdominal cramps and vomiting are common.

Diagnosis must be suspected in a case of diarrhea or abdominal pain, who is on antibiotics or has received them in last 2 months. Confirmation requires: (a) detec­tion of C. difficile toxin in stools by immunoassay, or (b) colonoscopy to visualize pseudomembranous plaques. Treatment includes: (a) discontinuation of suspected anti­biotics, (b) fluid and electrolyte correction, and (c) specific

TABLE 10.28: Post-injury immunization for TT**

*Followed by remaining doses for catch-up immunization

therapy with metronidazole (PO 20-40 mg/kg/d q6hr) or vancomycin (IV 40 mg/kg/d q6hr) for 7-10 days. Vancomycin is the only antibiotic, not known to cause PMC. Although most cases respond well, recurrence is common.

Botulism is a rare but potentially fatal disease with acute flaccid paralysis, due to a neurotoxin, produced by some strains of C. botulinum.

Pathogenesis: Spores of C. botulinum are ubiquitously present in soil, which may germinate in vivo (wounds) or in vitro (foods), under anaerobic conditions to produce a highly potent neurotoxin. According to the mode of infection, botulism may be divided into 3 distinct types:

a. Infant botulism due to ingestion of contaminated honey (as pre-lacteal feed) is often fatal, unless recognized and treated promptly.

b. Food-borne botulism due to ingestion of pre-formed toxin, present in spore-contaminated foods, e.g. home-canned or low-acid foods (sauces). Heating for 5 minutes destroys the pre-formed toxin.

c. Wound botulism due to in vivo germination of spores, multiplication of organisms and toxin production in infected wounds with dead tissue, e.g. crush injuries. Toxin spreads hematogenously to reach synaptic sites and block neuromuscular transmission.

Clinical presentation: Incubation period is shorter in food-borne or infant botulism, due to pre-formed toxins (18-36 hours), as compared to wound botulism (4-10 days).

Acute symmetrical descending flaccid paralysis is the cardinal feature of botulism, beginning with oculobulbar involvement, e.g. diplopia, ptosis, dysphagia, dysarthria and dysphonia and rapidly progressing downward to involve all muscles, including respiratory paralysis. In infants, weak cry and reduced spontaneous movements may be the first manifestation. Sensorium is normal, except in terminal cases due to hypoxia.

Other important features resemble atropine poisoning (anti-parasympathetic activity) with dry mouth, consti­pation and absence of sweating.

Outcome is poor in severe cases with death due to respiratory failure. Mild cases recover completely.

Diagnosis is suggested by: (a) typical clinical picture, i.e. descending flaccid paralysis with normal sensorium, and (b) characteristic EMG findings—brief, small, abundant motor-unit action potential in infants or potentiation of evoked muscle potential at high frequency in older children.

Confirmation requires: (a) detection of toxin in serum, wound site or feces, or (b) positive wound culture.

Management includes: (a) supportive therapy including ventilatory assistance, (b) debridement of dead tissue in contaminated wounds, (c) anti-toxin infusion (equine/

human, not freely available), and (d) antibiotics (in wound-botulism only) to control bacterial proliferation and further toxin production.

Aminoglycosides, which have neuromuscular toxicity, are contraindicated. Antibiotics are not recommended for food-borne or infant botulism, except to cover secondary infections.

Gas gangrene is rapidly progressive infection of soft tissue due to C. perfringens, with severe edema, necrosis, crepitations and a characteristic sweet odor in serosanguineous discharge. Pain is typically disproportionate to appearance of wound and systemic complications, e.g. shock and renal failure, develop rapidly.

Early debridement of wound with excision of necrotic tissue, IV antibiotic therapy with high-dose penicillin or clindamycin, and hyperbaric therapy (controversial role) may be life saving, but prognosis is poor.

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