Immunology vaccines

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Chapter 1: The immune response
Chapter 2: Routine childhood immunization
Chapter 3: Adolescent and adult vaccination
Chapter 4: Travel immunization
Chapter 5: Vaccine hesitancy
Chapter 6: The vaccine pioneers

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The impact of vaccines on public health has been, and is, enormous. No other intervention, perhaps, with the possible exception of clean water, has brought such profound benefits to the health of humanity as have vaccines. Vaccines have totally eradicated one scourge, smallpox, and have eliminated another from most of the world - polio. They have also eliminated from the Western Hemisphere measles as well as radically reduced many other serious vaccine-preventable infectious diseases from most of the world. Notes:i) The terms "vaccination" and "immunisation" have subtle differences in meaning. “Vaccination” specifically denotes the administration of a vaccine, which is nearly always successful, but in a minority of cases may not be successful in inducing a protective immune response. “Immunisation” denotes the successful induction of protective immunity. However, the two terms are generally used interchangeably and for most purposes can be used synonymously. ii) The term EPI, which stands for Expanded Programme on Immunization, is a WHO programme whose goal is to make as many vaccines as possible available to the children of the world for the prevention of childhood infections. Colloquially EPI vaccines refer to the vaccines routinely administered to infants and children. 2015-11-24 11-19-12 AM

Prof Barry D Schoub OMS MB BCh, MMed, MD, DSc, FRCPath, FCPath (SA), FRSSAf, MASSAf


Chapter 2

2.5 TETANUS DTaP: Infanrix© (GSK) DTaP-IPV-Hib: Pentaxim© (Sanofi-Pasteur) DTaP-IPV-HepB-Hib: Hexaxim© (Sanofi-Pasteur) DTaP-IPV-HepB-Hib: Infanrix Hexa© (GSK) Td: Diftavax© (Sanofi-Pasteur) TdaP-IPV: Adacel Quadra© (Sanofi-Pasteur) Boostrix tetra© (GSK)

THE ORGANISM Tetanus is an acute infectious disease characterised by a dramatic clinical presentation of muscle rigidity, especially of the jaw muscles (lockjaw, trismus, risus sardonicus) and back muscles (opisthotonos), spasms and seizures. Fatality rates are high even in developed countries with high quality intensive care facilities. The bacterium, Clostridium tetani, is a gram positive anaerobic slender rod-shaped organism with a terminal spore, giving it a characteristic drumstick appearance. While the bacterium is sensitive to heat and intolerant of oxygen, its spores are extremely hardy surviving autoclaving (121°C for 10-15 min) as well as being resistant to all antiseptic materials. The organism is widespread in soil and in the intestinal tracts of animals and poultry and hence dirty wounds, especially contaminated with soil or faeces, are particularly at risk. The organism secretes two toxins, tetanolysin, which is of doubtful significance, and tetanospasmin, which is an extremely potent neurotoxin – one of the most potent toxins known (minimal lethal dose for humans is 2.5 ng /kg!). The toxin binds to the motor endplates of motor nerves interfering with the release of neurotransmitters thus effectively blocking inhibitory impulses and resulting in unopposed muscle activity and hence the spasms and seizures. THE DISEASE The organism enters the body via wounds which are contaminated by soil or faeces or through unclean instruments and under relative anaerobic (low oxygen) conditions the spores germinate. The organism multiplies secreting neurotoxin which is absorbed into the bloodstream reaching the nerve endings. In the case of neonatal tetanus, the raw umbilical cord wound is the site of entry when unclean instruments are used and, as is still the practice in some communities, when cow dung is applied to the wound. The incubation period is generally 7 to 8 days (range: 3 to 21 days), the length being dependent on the distance from the wound to the central nervous system. The severity of disease is also dependent on this distance – the shorter the distance the more severe the disease. Muscle rigidity commences in the head and neck manifesting as lockjaw, neck stiffness and occasionally also spasm of the muscles of the glottis which may cause sudden death. Spasm of the back muscles (opisthotonos) and of the abdominal muscles follow in rapid succession. The disease is accompanied by pyrexia, sweating and raised blood pressure. In some cases severe spasms may result in fractures of the long bones. Spasms continue for 3 to 4 weeks and recovery may take several months. Case fatality rates vary from 10 to 70% and even in developed countries range from 10 to 20%. Localised tetanus, where the spasms are not generalised, carries a significantly lower mortality. THE VACCINE Tetanus toxoid vaccine is one of the oldest of human vaccines, first developed in 1924 and widely used in the Second World War. The vaccine is produced by growing the organism in liquid culture medium, inactivating the toxin with formaldehyde and then absorbing the toxoid onto aluminium salt. The toxoid comes in several formulations, tetanus toxoid alone TT, combined with diphtheria toxoid for administration to children less in six years of age DT, or with reduced diphtheria toxoid for children over six years and adults Td or combined with pertussis DTaP for infants and young children or Tdap for older (>6yrs) and adults. Protective immunity is incomplete after one dose but after two doses exceeds 90% and is close to 100% after three doses. Tetanus disease is virtually unknown in individuals who have received a full course of immunisation. Maternal antibodies cross the placenta and are protective to the newborn infant. The duration of immunity after a full course of immunisation is at least for 10 years. Tetanus toxoid is reasonably stable – retaining its potency even for months at 20°C; however it should be stored between 2 and 8°C. The vaccine must never be frozen and any vaccine which has been frozen should be discarded. ADMINISTRATION The vaccine is administered by intramuscular injection into the anterolateral aspect of the thigh in infants and the deltoid muscle in children and adults. For routine EPI administration it is given as part of a multi-antigen complex, pentavalent (DTaP, Hib,TIPV) or hexavalent (DTap, Hib,TIPV,HBV) at 6, 10 and 14 weeks with a booster at 18 months. Subsequent boosters should be given at six years and following that the 10 yearly intervals especially if there is exposure to agriculture, gardening, mining and similar activities. Pregnant mothers should receive vaccine approximately 2 weeks before delivery – preferably Tdap. Tetanus toxoid should be given intramuscularly for any wound, other than clean minor wounds, if there is uncertainty about having received a full course of immunisation within the previous five years. ADVERSE EVENTS AND CONTRAINDICATIONS Tetanus toxoid is an extremely safe vaccine and side-effects when they may occur are usually trivial. Pain and induration at the site of inoculation may be experienced. Rarely there may be an allergic response to the toxoid or components in the vaccine. If an allergic response to the vaccine has been experienced previously, a test dose can be given intradermally (with an anaphylactic kit on standby). Very rare cases of peripheral neuropathy and even Guillain Barre syndrome have been reported. MANAGEMENT OF TETANUS The management of a clinical case of tetanus is predominantly supportive in a high-care or intensive-care unit. It is imperative to maintain an airway and to control the spasms and seizures as well as to avoid nosocomial infections which are common this situation. Tetanus immunoglobulin (TIG) is recommended, given as a single dose of 3- to 5000 units intramuscularly as well as infiltrated into the wound. The antitoxin may be effective in inactivating circulating toxins but will have no effect on toxin already bound to the motor endplates. Antibiotics have no role in the treatment of the tetanus infection but may be of importance in the management of nosocomial infections.