Vincent Nacouzi
TETANUS
EPIDEMIOLOGY
The reported cases of tetanus worldwide are about a million cases per year. The mortality is close to 30% mostly in Africa and Asia. In the United States, tetanus is uncommon and mostly seen in temperate areas. Texas, California, and Florida report most cases annually.
Intravenous drug user has a disproportionate risk of contracting tetanus.
Only 30% of elderly Americans over the age of 70 years have adequate immunization; they also have the highest incidence of death from the disease.
PATHOPHYSIOLOGY
Tetanus is caused by Clostridium tetani, a gram-positive rod. The wound is often contaminated by the spore-forming organism. Later when oxygen tension decreases in the wound, as seen in crushed, devitalized tissue, the toxin-producing C. tetani develops.
Clostridium tetani produces two exotoxins: tetanospas-min, the most potent of both neurotoxins, is responsible for the clinical manifestations of tetanus. Incubation varies from 24 hours to over 30 days. Dissemination is initially hematogenous then via the nervous system.
Tetanospasmin acts on the motor endplates of skeletal muscle, in the spinal cord, in the brain, and in the sympathetic nervous system. This prevents the release of the inhibitory neurotransmitters glycine and gamma-amino butyric acid (GABA), resulting in loss of normal inhibitory control.
CLINICAL FEATURES
The clinical manifestations of tetanus are neuromus-cular irritability, muscular rigidity, violent contractions, and instability of the autonomic nervous system.
Wounds that become infected with toxin-producing C. tetani are most often puncture wounds, but can vary in severity from lacerations to minor corneal abrasion.
Local tetanus is manifested by rigidity of the muscles in proximity to the site of the wound and usually resolves after weeks without squeal. It may progress to generalized tetanus.
Generalized tetanus is the most common form of the disease.
The most frequent presenting complaints are pain and stiffness in the masseter muscles (lockjaw).
Nerves with short axons are affected initially; therefore, symptoms appear first in the facial muscles, with progression to the neck, trunk, and extremities.
Trismus manifest as a sardonic smile, hence the term “rhesus sardonicus.” Dysphagia, opisthotonus, and extension of lower extremities are also seen, but of importance, the mental status remains normal. This helps differentiate other pathologies.
Instability of the autonomic nervous system, mostly a hyper sympathetic state, typically occurs in the second week of clinical tetanus and presents as tachycardia, hypertension, diaphoresis, and fever.
Cephalic tetanus follows injuries to the head, and some cases of chronic otitis, resulting in dysfunction of the cranial nerves, most commonly the seventh. The prognosis is poor.
Neonatal tetanus occurs only if the mother is inadequately immunized. Most cases of neonatal tetanus arise from unsterile handling of the umbilical cord at the time of birth or the umbilical stump after birth. The infant is weak, irritable, and unable to suck.
DIAGNOSIS AND DIFFERENTIAL
Tetanus is a clinical diagnosis. There is no laboratory test to diagnose it.
Strychnine poisoning most closely mimics the clinical picture of generalized tetanus.
The differential diagnosis includes strychnine poisoning, serotonin syndrome, peritonitis, and malignant neuroleptic syndrome, dystonic reactions to the phenothiazines, hypocalcemic tetany, rabies, and temporomandibular joint disease.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Patients with tetanus should be managed in an intensive care unit due to the potential for respiratory compromise. Minimize stimuli to prevent reflex convulsive spasms. Debridement of the inciting wound, if present, is necessary to minimize further toxin production.
Tetanus immune globulin (TIG), 3000 to 6000 U intramuscularly in a single injection, should be given. TIG neutralizes circulating toxin but not toxin already fixed to the nervous system. Always give away from the tetanus vaccine site, and do not use the same syringe for both vaccine and immunoglobulin.
Always give before any wound debridement, because more exotoxin may be released during wound manipulation.
Antibiotics are of questionable value in the treatment of tetanus. If warranted, parenteral metronidazole (500 milligrams intravenously every 6 hours) is the antibiotic of choice. Do not use penicillin as it may potentiate the effects of tetanospasmin.
Midazolam (5–15 milligrams IV as a continuous drip to effect) is best to use and results in sedation as well as amnesia. Lorazepam can be used but should be avoided in prolonged and repeated doses since the diluent, glycol, can cause acidosis.
Neuromuscular blockade is often required to control ventilation and muscular spasm and to prevent fractures and rhabdomyolysis. Vecuronium, the agent of choice, is given (6–8 milligrams/h intravenously) because of its minimal cardiovascular side effects. Sedation during neuromuscular blockade is of primary importance.
The combined α- and β-adrenergic blocking agent labetalol (0.25–1 milligram/min continuous intravenous infusion, 0.3 to 1 milligrams/kg/h in children) has been used to treat the manifestation of sympathetic hyperactivity.
Propranolol is contraindicated because of its unopposed beta effects with sudden death cases reported.
Magnesium sulfate (70 milligrams/kg loading dose, then 1–4 grams/h intravenously) has been advocated as a treatment for this condition as well.
Morphine sulfate (0.5–1 milligram/kg/h) is also useful and provides sympathetic control without compromising cardiac output. Clonidine may be helpful in the management of cardiovascular instability.
Patients that recover from clinical tetanus must undergo active immunization (see Chapter 18, and Table 18-1, Recommendations for Tetanus Prophylaxis, for the treatment schedule).
RABIES
EPIDEMIOLOGY
Rabies, primarily a disease of animals, claims over 60,000 deaths annually, worldwide.
Ninety percent of transmission is due to dogs and where there is no canine control, wild animals accounted for almost 94% of the reported cases in decreasing order: raccoons; skunks; bats; foxes; and other wild animals, including rodents and lago-morphs. Rabid domestic animals included cats; cattle; dogs; horses and mules; sheep and goats; and other animals such as ferrets.
Bat exposure even without a documented bite may require rabies prophylaxis. Such exposure maybe as simple as awakening in a room with a bat, or witnessing a bat in a room with a mentally disabled person, a child, or an intoxicated person; all those may require prophylaxis.
In the United States most reports of rabies in wildlife far exceed those in domestic animals. Most other cases of human rabies diagnosed in the United States are attributable to infections acquired in areas of enzootic canine rabies outside of the United States; most persons with a case of rabies that originated in the United States have no history of an animal bite.
The following animals are almost never found to be rabid: rodents (squirrels, chipmunks, rats, mice, etc.) and lagomorphs (rabbits, hares, and gophers); therefore, postexposure prophylaxis may not be needed. Do contact the health officials for management.
PATHOPHYSIOLOGY
The rabies virus resides in the infected salivary glands of the animal. Once introduced, the incubation is 20 to 90 days where the virus remains close to the inoculation site.
Subsequently the virus spreads across the motor endplate, and ascends and replicates along peripheral nervous system to the spinal cord and central nervous system (CNS). Following CNS replication, the virus spreads outward by peripheral nerves to most tissues and organ systems.
CLINICAL FEATURES
Fever, malaise, headache, anorexia, nausea, sore throat, cough, and pain or paresthesia at the bite site (80%) are initial symptoms of human rabies and last 1 to 4 days.
Later, CNS involvement leads to restlessness and agitation, altered mental status, painful bulbar and peripheral muscular spasms, opisthotonos, and motor paresis.
DIAGNOSIS AND DIFFERENTIAL
Rabies is diagnosed clinically; there is no laboratory test for rabies. It should be suspected in any case of encephalitis.
Most confirmatory diagnoses are made by postmortem analysis of brain tissue. Cerebrospinal fluid (CSF) and serum antibody titers should be sent to laboratories skilled in rabies identification. Elevated CSF protein and a mononuclear pleocytosis are also seen.
The differential diagnosis includes other infectious encephalitis, polio, viral process, meningitis, brain abscess, cavernous sinus thrombosis, cholinergic poisoning, Guillain–Barre syndrome, and tetanus (normal mentation and normal CSF).
EMERGENCY DEPARTMENT CARE AND DISPOSITION
When rabies exposure is suspected: If the person is bitten, scratched, or exposed to saliva of a possible rabid animal, treatment begins with the assessment of true risk for rabies, notification of public health and animal control, and if at risk, the administration of postexposure prophylaxis.
Local wound care and debridement of devitalized tissue, if any, is important in reducing the viral inoculum and increasing oxygen tension in the tissue. Do not suture wounds of special concern, as this promotes rabies virus replication. Recall that the depth of the wound, the number of wounds, and their location increase the risk of developing the disease. Tetanus prophylaxis when needed should also be administered.
Awakening in a room with a bat has been associated with the development of rabies. For this reason, the CDC recommends rabies postexposure prophylaxis for all persons who have been exposed to a bat unless the bat is available for testing and is negative for evidence of rabies.
The CDC recommends that a healthy dog, cat, or ferret that bites a person should be confined and observed for 10 days.
Human rabies immune globulin (HRIG) is administered only once at the outset of therapy. The dose is 20 IU/kg, with half the dose (based upon tissue volume constraints) infiltrated locally at the exposure site and the remainder administered intramuscularly.
Human diploid cell vaccine (HDCV) for active immunization is available in two formulations of the same vaccine. The HDCV can be administered intramuscularly or intradermal in five 1-mL doses on days 0, 3, 7, and 14. Day 28 is no longer recommended by the Advisory Committee on Immunization Practices (ACIP).
Use only the regimens recommended by the US ACIP, from the CDC, because of their proven efficacy.
Preexposure prophylaxis does not eliminate the need for prophylaxis after a rabies exposure, but it does simplify it by reducing the number of doses needed.
The recommendations for postexposure prophylaxis should be followed exactly as given in the package insert. While there have been no failures in the United States, failures in other countries have been due to alterations in the method of administration or dosing interval.
Healthcare workers with mucous or non-intact skin exposed to a patient with suspected rabies should receive postexposure prophylaxis for rabies.
Ordinarily, dogs and cats involved in an attack on someone are quarantined for 10 days. If no signs become apparent within that period, the animal can be considered nonrabid.
State or local officials should be consulted regarding the risk of rabies in local animal populations before initiating rabies prophylaxis. This action may not be possible before the first treatment, but may affect subsequent treatments. Animal bites should be reported to the local animal control unit so that animals can be captured or quarantined for observation in a timely fashion.
The Centers for Disease Control and state and county health departments can provide assistance in the management of rabies complications. The rabies home page, which is produced and updated regularly by the Centers for Disease Control at www.cdc.gov/ncidod/dvrd/rabies, offers good update resources.
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 151, “Tetanus,” by Joel L. Moll and Donna L. Carden, and Chapter 152, “Rabies,” by David J. Weber, David A. Wohl, and William A. Rutala.