Gram-Positive Exotoxic Infections
Characteristics: Gram-positive, pleomorphic rods. Aerobic.
Habitat/Transmission: Habitat is human throat. Transmission is via respiratory droplets or exudate from infected skin lesions.
Clinical Features: Organism invades and creates a pseudomembrane (nose, throat, etc.) from which it excretes exotoxin. This spreads via blood, primarily impacting cardiac tissue and nervous system. Death due to myocarditis occurs as a result of conduction abnormalities and rhythm disturbances or due to cardiac muscle failure. Nervous system involvement variable. Organism can infect via chronic skin ulcers or surgical wounds. Individual develops immunity to toxin. Cutaneous diphtheria can be reservoir for respiratory diphtheria, vice-versa.
Management: Passive antitoxin from horses neutralizes toxin. Penicillin G kills organism but doesn’t eliminate toxin. Pseudomembrane requires mechanical assistance (tracheostomy, bronchostomy). Myocarditis/nervous system treated pharmacologically or mechanically.
Prevention: Series of Immunization with formalin-inactivated toxin beginning at 2 months of age, adult boosters every 10 years.
- (1) Only C. diphtheriae strains containing a specific lysogenic bacteriophage produce exotoxin. Strains without this phage are nontoxinogenic and theoretically not capable of causing diphtheria.
- (2) Synthesis and toxin release occurs only when a specific concentration of inorganic iron (ferrous or ferric) is present in the growth medium.
- (3) Diphtheria toxin is an A-B exotoxin which inhibits protein synthesis by adding ADP-ribose to EF-2. Subunit A ADP-ribosylates, and Subunit B binds the toxin to cell surface receptors. (see D3J 1BBD-222, or Sherris fig 17-1)
Characteristics: Gram-positive, spore-forming rods. Anaerobic.
Habitat/Transmission: Habitat is soil and excreta of man and animals. Organism enters through traumatic breaks in skin.
Pathogenesis: Tetanus toxin (tetanospasmin) is an A-B water soluble exotoxin produced by vegetative cells at the wound site. It is transported retrograde through axonal processes to the spinal cord, it interferes with synaptic transmission by preferentially inhibiting release of inhibitory neurotransmitters; the net effect is to block inhibitory neurons and produce spastic paralysis. The toxin is a protease and has its effect by cleaving the proteins involved in mediator release.
Clinical Features: Incubation period is ~3-21 days. The further toxin must travel along nerve to reach CNS, the more prolonged the incubation period. Spasmodic or sustained involuntary contraction of muscle groups results. In over 50% of cases presenting symptom is trismus (motor disturbances with difficulty opening mouth, "lockjaw" Þ sardonic smile). Patient is conscious and experiences excruciating pain.
Diagnosis: Lab studies are useless, diagnosis is therefore based on history of an injury, followed by syndromes.
Treatment: Neutralization of circulating toxin with Human tetanus immunoglobulin (TIG), eradication of infected focus to prevent further toxin production, sedation for control of seizures.
Prevention: Immunization with tetanus toxoid. This is especially easy considering there is only 1 antigenically distinct form of the organism (as opposed 7 forms in botulism). Booster every 10 years.
Disease: Botulism Þ food poisoning (enterotoxicosis)
Characteristics: Gram-positive, spore-forming rods. Anaerobic bacillus.
Habitat/Transmission: Habitat is the soil. Organism and toxin transmitted in improperly preserved food.
Pathogenesis: Botulinum toxin is absorbed from the gut and carried via the blood to peripheral nerve synapses, where it irreversibly blocks release of acetylcholine at cholinergic synapses. It is a protease that cleaves the proteins involved in acetylcholine release. The toxin is a polypeptide encoded by a lysogenic phage. Along with tetanus toxin, it is among the most toxic substances known. There are eight immunologic types of toxin; types A, B, and E are the most common in human illness.
Clinical Features: Symptoms occur within 18-96 hours. Hallmark is acute, flaccid paralysis which begins with the muscles of the head, face, throat and then extends symmetrically to involve trunk and extremities. Progressive paralysis causes death. If maintained on life-support, recovery may take months or years by growth of new nerve endings. Infant botulism, occuring when spores germinate in the newborn gut, may be mistaken for sudden infant death syndrome (SIDS). Honey may be spore source.
Diagnosis: Demonstration of toxin in serum or feces. Mouse toxin-neutralization test.
Treatment: Antitoxin to types A, B, and E made in horses. Respiratory support may be required.
Prevention: Observing proper food preservation techniques, and cooking all home-canned food.