6. Diphtheria

In the pre-immunisation era, diphtheria was predominantly a disease of children aged under 15 years; most adults acquired immunity without experiencing clinical diphtheria. Asymptomatic carriage was common (3–5 percent) and important in perpetuating both endemic and epidemic diphtheria. The global incidence of diphtheria dropped dramatically during the 20th century. Immunisation played a large part but may not be wholly responsible for this reduction (see Figure 6.1). The estimated total number of diphtheria cases globally fell from just under 100,000 cases in 1980 to around 4,500 in 2015, but increased to over 16,500 cases in 2018.[4]

Diphtheria remains a significant health issue in countries with low immunisation coverage. Around 14 percent of children globally are not fully immunised against diphtheria and all countries have pockets of unvaccinated children.[5] Most cases of diphtheria reported during 2011–2015 were in South-East Asia, in particular India and Indonesia, but under-reporting has been shown for Africa and Eastern Mediterranean regions.[5]

Figure 6.1: Diphtheria global annual reported cases and DTP3* immunisation coverage, 1980–2018

Diphtheria infection was common in New Zealand until the 1960s. The last case of toxigenic respiratory diphtheria was reported in 1998.[9] Low numbers of cutaneous toxigenic diphtheria are regularly notified in New Zealand: two confirmed cases were notified in 2015 in refugees from Afghanistan[10] and one case was notified in 2019 in an immunised child from Papua New Guinea.

Non-toxigenic C. diphtheria isolates continue to be identified; for example, there were seven throat and 41 cutaneous non-toxigenic isolates and seven from other sites in 2019 (ESR, 8 June 2020). These strains do not cause diphtheria disease.

Travel to endemic countries is an important risk factor for infection, but transmission within New Zealand can occur to susceptible contacts of cutaneous cases. Tattooing practices in the Pacific Islands have also been implicated in outbreaks in New Zealand.[11]

The 2005–2007 National Serosurvey of Vaccine Preventable Diseases found that 61 percent of 6–10-year-olds, 77 percent of 11–15-year-olds, 71 percent of 16–24-year-olds, 48 percent of 25–44-year-olds and 46 percent of ≥45-year-olds had presumed protective levels of diphtheria antibody.[12] The decline apparent with age suggests there is likely to be a large and increasing pool of older adults who may be susceptible to diphtheria in New Zealand, despite the introduction of adult tetanus and diphtheria (Td) vaccination in 1994.

For details of diphtheria notifications, refer to the most recent ESR notifiable disease annual tables and reports.

Funded diphtheria vaccines

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

Other vaccines

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

• Tdap: Adacel (Sanofi)
• Tdap-IPV: Adacel Polio (Sanofi).

Immunity against toxigenic 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 15.4.2.

Herd immunity

Immunisation is more effective at preventing disease, by neutralising diphtheria toxin, than preventing infection. Herd immunity is created by reducing carriage and transmission from symptomatic patients.[13, 14] To prevent major community outbreaks, it has been suggested that 70 percent or more of the childhood population must be immune to diphtheria.[15, 16] Herd immunity in adults is likely to depend on the size of the reservoir of disease in children.[1] 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 required. 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 older adult population.[5] WHO identified that adults in countries with long-standing childhood immunisation programmes were likely to be susceptible without booster doses to overcome waning immunity due to lack of exposure to diphtheria. Waning immunity contributed to the high number of cases in adults observed during the outbreak in the former Soviet Union.[17]

Despite apparent immunity gaps, there has been minimal disease in high-income countries, suggesting that the established correlates of seroprotection based on antitoxin levels may not be reliable guides for protection and that other factors may be operating.[18] For example, a high proportion of the adult German population have low antibody levels, indicating susceptibility, yet diphtheria outbreaks have not occurred despite Germany’s relative geographical proximity to high rates of disease in the former Soviet Union.[19]

The duration of protection after Tdap boosters is unknown, but the results of an Australian study have shown that five years after the Tdap booster dose, 94.4 percent of adults had seroprotective levels of antibodies against diphtheria, compared with 93.7 percent who received Td vaccine.[20] It has been predicted that 95 percent of the adult population in the US would maintain seroprotection for more than 30 years without requiring further booster doses.[21]

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017 (2nd edition).

Store at +2°C to +8°C. Do not freeze. DTaP-IPV-HepB/Hib and Tdap should be stored in the dark.

The dose of DTaP-IPV-HepB/Hib, DTaP-IPV or Tdap vaccine is 0.5 mL, administered by intramuscular injection (see section 2.2.3).

Co-administration with other vaccines

DTaP-IPV-HepB/Hib, DTaP-IPV or Tdap vaccine can be administered simultaneously (at separate sites) with other vaccines or IGs.

A primary course of diphtheria vaccine is given as DTaP-IPV-HepB/Hib (Infanrix-hexa) at ages 6 weeks, 3 months and 5 months, followed by a dose of DTaP-IPV (Infanrix-IPV) at age 4 years (Table 6.1). A booster is given at age 11 years (school year 7), which includes a pertussis component given as the vaccine Tdap (Boostrix).

If a course of immunisation is late or interrupted for any reason, it may be resumed without repeating prior doses (see Appendix 2).

For previously unimmunised individuals aged 10 years and older, a primary immunisation course consists of three doses of a diphtheria toxoid-containing vaccine at intervals of not less than four weeks (see Appendix 2). For children aged under 18 years, a booster dose is recommended at least six months after the third dose.

Children aged under 18 years may receive Tdap (funded from age 7 to under 18 years); adults aged 18 years and older may receive Td (funded) or Tdap (unfunded). Although Tdap and Td are not approved for use (registered) as a primary course, there are expected to be no safety concerns.

Studies overseas show that many adults lack protective levels of the antitoxin, and this has led to concern about waning immunity and recommendations for booster doses beyond childhood (see also section 6.3.2). Most authorities recommend maintaining diphtheria immunity by periodic reinforcement using a combined Td vaccine.[1] A single booster dose of Tdap induces seroprotective levels of antibodies to diphtheria and tetanus in virtually all children and adolescents, and in a high proportion of adults and elderly individuals at approximately one month post‐vaccination, irrespective of their vaccination history.[22]

Tdap is recommended and funded:

• as a booster dose to all adolescents at school year 7 or age 11 years
• as a booster dose for vaccination of individuals aged 65 years old
• as a single dose for catch-up vaccination of individuals aged 45 years old who have not had four previous tetanus-containing doses.

These age-specific recommendations may facilitate the linkage of adult immunisation to the delivery of other preventive health measures.

Booster doses before travel

If someone is travelling to an area endemic for diphtheria, or there is another reason to ensure immunity, a booster dose is recommended (but not funded) if it is more than 10 years since the last dose. For website sources on travel vaccines, see Appendix 8.

Pregnant women should receive a dose of Tdap in every pregnancy so that antibodies can pass to the fetus to provide pertussis protection from birth (funded when given any time in second or third trimester). It is recommended to be given from 16 weeks’ gestation of every pregnancy, preferably in the second trimester to protect both the mother and her infant from pertussis (see section 16.5.2).[23]

Tdap vaccine may also be given to pregnant women when catch-up is needed for an under-immunised woman, or for management of a tetanus-prone wound (see section 20.5.5).[23, 24]

Tdap vaccines can be given to breastfeeding women.[24]

Diphtheria toxoid-containing vaccines are funded for (re)vaccination of eligible patients as follows, including prior to planned or following immunosuppression. See also section 4.3.2.

DTaP-IPV-HepB/Hib (Infanrix-hexa) and DTaP-IPV (Infanrix-IPV)

Up to an additional four doses (as appropriate) of DTaP-IPV-HepB/Hib (for children aged under 10 years) or DTaP-IPV are funded for (re)vaccination of patients:

• post-HSCT or chemotherapy
• pre- or post-splenectomy
• pre- or post-solid organ transplant
• undergoing renal dialysis
• prior to planned or following other severely immunosuppressive regimens.

Up to five doses of DTaP-IPV-HepB/Hib (for children aged under 10 years) or DTaP-IPV are funded for children requiring solid organ transplantation.

Tdap (Boostrix)

An additional four doses (as appropriate) of Tdap (Boostrix) are funded for patients:

• post-HSCT or chemotherapy
• pre- or post-splenectomy
• pre- or post-solid organ transplant
• undergoing renal dialysis
• prior to planned or following other severely immunosuppressive regimens.

There are no specific contraindications to diphtheria vaccine (as Tdap or DTaP), except for anaphylaxis to a previous dose or any component of the vaccine.

Most other cases of hypersensitivity that have been reported for tetanus-containing vaccines were in individuals who have had an excessive number of booster injections outside the guidelines noted above (see section 20.6.2).

See section 15.6.2 for precautions for pertussis-containing vaccines and section 20.6.2 for precautions for tetanus-containing vaccines.

All contacts, after cultures have been taken and regardless of immunisation status:  

• A single dose of intramuscular benzathine penicillin 
  • for contacts under 6 years of age, 600,000 units 
  • for contacts 6 years of age or over, 1.2 million units

or 

• Oral Azithromycin, treat for total 5 days 
  • Children: 10 mg/kg as a single dose on the first day followed by 5 mg/kg/day on days 2-5. For children weighing >45 kg, dose as adult. 
  • Adults: Total dose of 1.5g taken as 500mg on day 1, then 250mg daily on days 2-5 or alternatively 500mg for 3 days 

 or 

• Oral erythromycin, treat for 7 to 10 days  
  • children: 30-50 mg/kg/day in equally divided doses four times daily (every 6 hours). Can be also given twice daily if needed.  
  • adults 1,600 mg/day in equally divided doses 400mg four times daily (every 6 hours). Can be also given twice daily if needed.

• Close contacts are recommended to receive chemoprophylaxis even if the index case has received eradication therapy. 
• A pragmatic choice of dosage may be decided upon on further discussion including infection disease physicians and pharmacists. 

Contacts with a positive culture: two follow-up cultures should be obtained at least 24 hours after completion of therapy. If cultures are still positive, discuss further management with an infectious disease physician. The primary health care practitioner should be kept informed of the management of contacts and laboratory results.

All close contacts should also be offered a complete course of vaccine or a booster according to the following schedule.

• Fully immunised children up to and including 6 years of age who have only received three doses of diphtheria toxoid-containing vaccine: give one injection of a DTap-IPV.
• Fully immunised individuals aged 7 years and older who have not received a booster dose of a diphtheria toxoid-containing vaccine within the last five years: give one injection of Tdap – funded if aged 10–17 years; unfunded if aged 18 years or older (see section 6.5).
• Unimmunised individuals: see Appendix 2.

Contacts who have a positive laboratory result should be isolated as if they are a case until proven bacteriologically negative.

For further information, see the ‘Diphtheria’ chapter of the Communicable Disease Control Manual.

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