Tetanus - PHTH1012 013 PDF

Dr. Karen Roye-Green Tetanus First described by Hippocrates Etiology discovered in 1884 by Carle and Rattone Passive immunity used for treatment and prophylaxis during World War I Tetanus toxoid first widely used during World War II Clostridium tetani Anaerobic gram-positive, sporeforming bacteria S...

Dr. Karen Roye-Green Tetanus First described by Hippocrates Etiology discovered in 1884 by Carle and Rattone Passive immunity used for treatment and prophylaxis during World War I Tetanus toxoid first widely used during World War II Clostridium tetani Anaerobic gram-positive, sporeforming bacteria Spores found in soil, dust, animal feces; may persist for months to years Multiple toxins produced with growth of bacteria Tetanospasmin estimated human lethal dose = 2.5 ng/kg Clostridium tetani Bacterium is sensitive to heat and cannot survive in presence of oxygen. Spores are resistant to heat ,ethanol, phenol, formalin but sensitive to iodine, glutaraldehyde and hydrogen peroxide. Spores are found in faeces of horses, sheep, cattle,dogs, cats,rats,guinea pigs and chickens. Spores can also be found on skin. Tetanus pathogenesis Usually enters the body through a wound. Toxin are produced when spores germinate and disseminate via blood and lymphatics Toxins act at the central nervous system (peripheral motor end plate ,spinal cord, brain,and sympathetic nervous system). Tetanus pathogenesis The multiplying organisms produce the tetanus toxin ,a polypeptide. This consist of binding(B) domain and an enzymatic (A) domain which is cleaved by the bacterium. The biological activity resides in the A portion where as the B subunits binds to the target cells but are biologically inactive Tetanus Pathogenesis The B domain interacts with ganglioside at neuromuscular junctions,both locally and distally, and enables the A domain to enter the cytoplasm of the neuron. The tetanospasmin is transported in a retrograde manner to the cell body in the ventral horns of the spinal cord. Tetanus pathogenesis Within the neurons the tetanus toxin cleaves synaptobrevin,a protein component of synaptic vesicles ,and prevents the release of neurotransmitters at the presynaptic membrane. Disinhibition of spinal cord reflex arcs,due to prevention of release of neurotransmitter from presynaptic inhibitory cells and motor neurons. Tetanus pathogenesis Excitatory reflexes,freed from inhibition,thus lead to multiple,intense muscle spasms. Tetanus toxins also interferes with presynaptic acetylcholine release at the neuromuscular junction & disinhibits sympathetic reflexes at the spinal level,producing autonomic dysfunction. Tetanus pathogenesis Anaerobic conditions allow germination of spores and production of toxins Toxin binds in central nervous system Interferes with neurotransmitter release to block inhibitor impulses Leads to unopposed muscle contraction and spasm Tetanus Clinical Features Incubation period; 8 days (range, 3-21 days) Four clinical forms: Local (not common), cephalic (rare),neonatal, generalized (most common) Generalized tetanus: descending symptoms of trismus (lockjaw), difficulty swallowing, muscle rigidity, spasms Spasms continue for 3-4 weeks; complete recovery may take months Tetanus clinical features The further the injury site is from the CNS,the longer the incubation period. The shorter the incubation period, the higher the chance of death. In neonatal tetanus, symptoms usually appear from 4 to 14 days after birth, averaging about 7 days. Local tetanus Consist of fixed muscle rigidity and painful spasms, sometimes lasting weeks or months before gradually subsiding,confined to on area close to site of the injury. May precede the onset of generalized tetanus,which occurs when enough toxin gains access to CNS. Cephalic tetanus Particular form of localized tetanus associated with wounds to the head or face or with chronic otitis media. There is involvement of the cranial nerves ,especially in the facial areas. Generalized tetanus may follow. Generalized tetanus Starts with rigidity & spasms of the masseter muscles, causing trismus or lock jaw risus sardonicus( a grimace through clenched teeth & closed mouth with wrinkled forehead and raised eyebrows). First the neck,then the thorax,back & extremities,become rigid & go into spasm producing opisthotonos, abdominal contraction. Generalized tetanus Tetanospasms are intermittent ,irregular & unpredictable,triggered by external stimuli e.g sudden noise or puff of cold air or internal stimulus of a distended bladder or bowel. Pharyngeal spasm causes dysphagia & spasm of the glottis may cause immediate asphyxiation &death. May result in vertebral & long bone fractures Generalized tetanus Abnormalities of the ANS including hypotension & hypertension, arrhythmias and flushing. Elevated temperature , sweating, episodic rapid heart rate. Spasms may occur frequently and last several minutes. Spasms continue for 3-4 weeks. Complete recovery may take months. Neonatal Tetanus Usually occurs through infection of the unhealed umbilical stump,particularly when the stump is cut with an unsterile instrument. Starts with generalized weakness,poor sucking & irritability, followed by trismus and tetanospasms. Higher death rate than other age groups Neonatal Tetanus Generalized tetanus in newborn infant Infant born without protective passive immunity High fatality rate without therapy Estimated >215,000 deaths worldwide in 1998 Tetanus Complications Laryngospasm Fractures Hypertension Nosocomial infections Pulmonary embolism Aspiration Death Tetanus Complications Nosocomial infections are common because of prolonged hospitalization. Secondary infections may include sepsis from indwelling catheters, hospital-acquired pneumonia, and decubitus ulcers. Pulmonary embolism is particularly a problem in drug users and elderly patients. Aspiration pneumonia is a common late complication. Tetanus Complications Laryngospasm( spasm of the vocal cords) and or spasms of the muscles of respiration leads to interference with breathing. Fractures of the spine or long bones may result from sustained contractions and convulsion. Hyperactivity of the autonomic nervous system may lead to hypertension and or an abnormal heart rhythm. Tetanus Epidemiology Reservoir Soil and intestine of animals and humans Transmission Contaminated wounds Tissue injury Temporal pattern Peak in summer or wet season Communicability Not contagious Tetanus Epidemiology Occurrence is worldwide ,but most often in hot, damp climates with soil rich in organic matter. Transmission is primarily by contaminated wounds. Tetanus may follow elective surgery, burns, deep puncture wounds,crush wounds, otitis media, dental infection, animal bites, abortion and pregnancy. Tetanus Epidemiology Acute wounds are the portal of entry in 80% of cases,with the remainder associated with chronic decubitus ulcers,gangrene,abscesses,or parenteral drug abuse. In developed countries ,most cases are in patients over the age of 60: this is one of several indicators that waning immunity is an important risk factor. Tetanus—United States, 1947-2002 700 600 Cases 500 400 300 200 100 0 1950 1960 1970 1980 1990 2000 Cases Tetanus—United States, 1980-2002 100 90 80 70 60 50 40 30 20 10 0 1980 1985 1990 1995 2000 Cases Tetanus—United States, 1980-2002 Age Distribution 1000 900 800 700 600 500 400 300 200 100 0