5/28/04 Bacterial Vaccines I LECTURE OUTLINE I. CASE HISTORY A man runs across a football field, feels something jab him in the foot and falls down. He plucks a rusty nail out of his foot and forgets about it. Two weeks later, his jaw becomes rigid. II. DISEASE: TETANUS "lockjaw" A. CHARACTERISTICS: An anaerobic infection at a site of injury and subsequent neurotoxin-related symptoms. Exotoxin causes painful muscular contractions (especially of the neck and jaw). First symptom may be abdominal rigidity. Facial expression "risus sardonicus." Fatality may vary from 30-90% depending upon age, length of incubation and therapy given. Spasms can occur for 3-4 weeks. Can take months to recover. B. AGENT: Clostridium tetani. An anaerobic gram-positive bacilli. Spore-former. C. HOST & HIGH RISK POPULATIONS Host: Humans, especially aged over 60!! D. VECTOR & TRANSMISSION Vector: Animals and humans (normal bowel flora) Transmission: through injury sites (especially puncture wounds (38%), lacerations (37%), and gardening wounds [spores]. Any deep injury contaminated with soil, animal/human feces or street dust. E. INCIDENCE Recent number of cases (USA cumulative): 1986 [67], 1987 [39], 1992 [45], 1993 [48], 1997 [50], 1998 [41], 1999 [40], 2000 [35], 2001 [27] F. IMMUNITY AFTER ACTIVE DISEASE: NO!!! III. TREATMENT Tetanus Immune Globulin and TD (Td) booster. But, even with treatment, the fatality rate is 30%!!! 1
Tetanus Wound Management Clean, minor wounds All other wounds Vaccination History Td TIG Td TIG Unknown or <3 doses 3+ doses * ** *, if >10 years since last dose **, if >5 years since last dose IV. VACCINE A. TYPE OF VACCINE: Toxoid. Part of DTaP. Formaldehyde deactivated toxin. Tripedia (Aventis Pasteur, $17.12), Infanrix (Glaxo SmithKline, $18.50) and TriHIBit (Aventis Pasteur, $37.32). Or, as DT and dt boosters. B. SCHEDULE AND ROUTE OF ADMINISTRATION Route: IM Schedule: Children: Given as part of DTaP to children. Given at 2, 4, 6, and 15-18 months. Booster 4-6 years old (school entry), recommended 11-12 years if 5 years since last dose. Adults: Booster (dt) given every 10 years or sometimes given as T-booster alone. It may be given earlier in the case of a high risk wound, as outlined above. Cost: trivalent $16-18/dose C. EFFICACY AND DURATION OF IMMUNITY Efficacy: 90-99%. Vaccine failure 4 per million. Duration: 10 years. D. COMPLICATIONS Local: Swelling and pain: 30-50%, self-limited. General: CNS complications (peripheral neuropathy, paralysis of nerves) rare: 0.4 per million. Concurrent use with chloramphenicol interferes with immune response. E. CONTRAINDICATIONS Anaphylactic reaction to a prior dose of the vaccin3e or any of its components. Encephalopathy within 7 days of a previous dose. 2
Precautions: Severe acute illness Underlying unstable, evolving neurologic disorder Conditions from a prior dose: fever of 105 deg F within 48 hrs with no other cause collapse or shock-like state within 48 hrs Persistent, inconsolable crying lasting over 3 hrs, within 48 hrs Seizure or convulsion within 72 hrs Guillian-Barre syndrome within 6 weeks 3
LECTURE OUTLINE I. CASE HISTORY 174 cases of a disease were noted in Seattle during an outbreak in 1974. All but 27 were in the adult skid-row population. Twelve of the cases developed toxin myocarditis, 3 had neuropathy, 6 had conjunctivitis, and 3 died. Symptoms were of a cutaneous nature, this disease may also manifest itself by causing a greyish "pseudomembrane" in the throat. II. DISEASE: DIPHTHERIA A. CHARACTERISTICS: A localized infection with nerve damage done by an exotoxin. Acute disease of tonsils, pharynx, conjunctiva and nose. A characteristic pseudomembrane, greyish in color, may develop in the throat with a surrounding dull red inflammatory zone. In young children, laryngeal diphtheria is serious. Inapparent cases far outnumber symptomatic cases. Cutaneous diphtheria: lesions appear like impetigo. Mostly in adults. Late effect of infection: Effect of toxin. (2-6 weeks later) myocarditis, nerve palsy. Case fatality rate 5-10%. B. AGENT: Corynebacterium diptheriae. Gram-positive bacteria. C. HOST & HIGH RISK POPULATIONS Host: Humans. Adults not immunized or with waning immunity. Children who are not immunized <15 years. D. VECTOR & TRANSMISSION Vector: Humans Transmission: Direct contact with patient or carrier. Indirect contact (rarely) fomites. E. INCIDENCE Recent number of cases (USA cumulative): 1986 [2], 1987 [3], 1992 [4], 1993 [0], 1997 [4], 1998 [1], 1999 [1], 2001 [2], cutaneous diphtheria: 60-100 cases/yr. F. IMMUNITY AFTER ACTIVE DISEASE: Extremely variable. III. TREATMENT Antitoxin (passive IgG), only neutralizes circulating toxin. Duration 15 days-3 weeks. Also treat with erythromycin or procaine penicillin G. Household contacts get booster and antibiotics. IV. VACCINE A. TYPE OF VACCINE: Toxoid. Detoxified by formaldehyde (loses virulence, but maintains antigenicity). Part of DTaP or DT, dt, as with tetanus toxoid. B. SCHEDULE AND ROUTE OF ADMINISTRATION Route: IM Schedule: As with DTaP. Booster every 10 years, given as DT or Td. Likelihood of adverse effects increases if the booster is given more frequently. 4
C. EFFICACY AND DURATION OF ACTION Efficacy: >97% ([Ab] > 0.1 IU of antitoxin/ml) Duration: approximately 10 years D. COMPLICATIONS Tenderness at site. Fever, anaphylaxis and neurological complications can occur but are rare. E. CONTRAINDICATIONS Anaphylactic reaction to a prior dose of the vaccine or any of its components. Encephalopathy within 7 days of a previous dose. Precautions: Severe acute illness Underlying unstable, evolving neurologic disorder Conditions from a prior dose: fever of 105 deg F within 48 hrs with no other cause collapse or shocklike state within 48 hrs Persistent, inconsolable crying lasting over 3 hrs, within 48 hrs Seizure or convulsion within 72 hrs Guillian-Barre syndrome within 6 weeks 5