5 Diphtheria

5.4 Vaccines

Diphtheria toxoid is prepared from cell-free purified diphtheria toxin treated with formaldehyde. It is a relatively poor immunogen, which, to improve its efficacy, is usually adsorbed onto an adjuvant, either aluminium phosphate or aluminium hydroxide. Diphtheria toxoid is only available as a component of combination vaccines (in New Zealand as DTaP-IPV-HepB/Hib, DTaP-IPV, Tdap and Td).

See Appendix 1 for the history of diphtheria toxoid-containing vaccines in New Zealand.

5.4.1 Available vaccines

Funded diphtheria vaccines

The diphtheria toxoid-containing vaccines funded as part of the Schedule are as follows.

DTaP-IPV-HepB/Hib (Infanrix-hexa, GSK): diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B and Haemophilus influenzae type b vaccine, which contains: ​
  • not less than 30 IU of diphtheria and 40 IU of tetanus toxoids and three purified Bordetella pertussis antigens (25 µg of pertussis toxoid; 25 µg of filamentous hemagglutinin; 8 µg of pertactin, a 69 kilodalton outer membrane protein) adsorbed onto aluminium salts
  • three types of inactivated polio viruses: 40 D-antigen units of type 1 (Mahoney), 8 D-antigen units of type 2 (MEF-1) and 32 D antigen units of type 3 (Saukett)
  • 10 µg of purified major surface antigen (HBsAg) of the hepatitis B virus
  • 10 µg of purified polyribosyl-ribitol-phosphate capsular polysaccharide (PRP) of Haemophilus influenzae type b (Hib), covalently bound to 20–40 µg tetanus toxoid (T), adsorbed onto aluminium salts
  • ​lactose, sodium chloride, Medium 199, potassium chloride, disodium phosphate, monopotassium phosphate, polysorbate 20 and 80, glycine, formaldehyde, neomycin sulphate and polymyxin B sulphate, which are also present as other components or as trace residuals from the manufacturing process.
DTaP-IPV (Infanrix-IPV, GSK): diphtheria, tetanus, acellular pertussis and inactivated polio vaccine, in the same quantities as for Infanrix-hexa above. Other components and residuals include sodium chloride, aluminium salts, Medium 199, potassium chloride, disodium phosphate, monopotassium phosphate, polysorbate 80, glycine, formaldehyde, neomycin sulphate and polymyxin B sulphate.

Tdap (Boostrix, GSK): a smaller adult dose of diphtheria toxoid and pertussis antigens together with tetanus toxoid. Tdap contains not less than 2 IU of diphtheria toxoid, not less than 20 IU of tetanus toxoid, 8 µg of pertussis toxoid, 8 µg of filamentous hemagglutinin and 2.5 µg of pertactin, adsorbed onto aluminium salts. Other components and trace residuals include sodium chloride, formaldehyde, polysorbate 80 and glycine.

Td (ADT Booster, Seqirus (NZ) Ltd): a smaller adult dose of diphtheria toxoid together with tetanus toxoid. Td contains not less than 2 IU of purified diphtheria toxoid and not less than 20 IU of purified tetanus toxoid. Other components and residuals include aluminium hydroxide, sodium chloride and sodium hydroxide.

Other vaccines

Other diphtheria toxoid-containing vaccines registered (approved for use) and available (marketed) in New Zealand are:

5.4.2 Efficacy and effectivenessTop

Immunity against diphtheria occurs via an antibody‐mediated response to the diphtheria toxin and is primarily of the IgG type. Antitoxin antibodies can pass through the placenta to provide passive immunity to the newborn.

Although there are no randomised controlled studies on the efficacy of the vaccine, between 87 and 98 percent protection has been demonstrated using population-based analyses. Immunised cases have been shown to have less severe disease, as highlighted during the outbreak in the former Soviet Union.

Vaccines combining pertussis antigens with diphtheria and tetanus toxoids have been gradually introduced into immunisation schedules throughout the world. Immunogenicity data for these combination vaccines is discussed in section 14.4.2.

Herd immunity

Although immunisation is more effective at preventing disease than preventing infection, it does create herd immunity and reduces carriage and therefore transmission.11 To prevent major community outbreaks, it has been suggested that 70 percent or more of the childhood population must be immune to diphtheria.12, 13 This may explain the control of diphtheria in New Zealand despite historically relatively poor coverage.

Duration of immunity

Diphtheria antitoxin levels decline over time in children after they have received a primary series of vaccines and a booster dose is given. In countries where diphtheria immunisation is common practice and high coverage rates are achieved, there will be no natural boosting from circulating disease, and antitoxin levels declining with increasing age may result in a susceptible adult population.14

Despite this, there has been minimal disease in developed countries, suggesting that antibody levels may not be a reliable guide to protection and that other factors may be operating.15 For example, a high proportion of the adult German population have low antibody levels, indicating susceptibility, yet this has not led to diphtheria outbreaks despite Germany’s relative geographical proximity to the former Soviet Union.16

The duration of protection after Tdap boosters is unknown, but the results of an ongoing Australian study have shown that five years after the Tdap booster dose, 94.4 percent of adults had seroprotective levels of antibodies, compared with 93.7 percent who received Td vaccine.17

5.4.3 Transport, storage and handlingTop

Transport according to the National Guidelines for Vaccine Storage and Distribution.18 Store at +2oC to +8oC. Do not freeze.

DTaP-IPV-HepB/Hib and Td should be stored in the dark.

DTaP-IPV-HepB/Hib (Infanrix-hexa) must be reconstituted by adding the entire contents of the supplied container of the DTaP-IPV-HepB vaccine to the vial containing the Hib pellet. After adding the vaccine to the pellet, the mixture should be shaken until the pellet is completely dissolved. Use the reconstituted vaccine as soon as possible. If storage is necessary, hold at room temperature for up to eight hours.

5.4.4 Dosage and administrationTop

The dose of DTaP-IPV-HepB/Hib, DTaP-IPV, Tdap or Td vaccine is 0.5 mL, administered by intramuscular injection (see section 2.3).

Co-administration with other vaccines

DTaP-IPV-HepB/Hib, DTaP-IPV, Tdap or Td vaccine can be administered simultaneously (at separate sites) with other vaccines or immunoglobulins. (See also section 14.4.4 for information about co-administration of DTaP-IPV-HepB/Hib and PCV13.)