Td – tetanus-diphtheria toxoid là gì

Information about diphtheria disease, vaccines and recommendations for vaccination from the Australian Immunisation Handbook.

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Recently added

This page was added on 06 June 2018.

Updates made

This page was updated on 08 March 2022. View history of updates

Vaccination for certain groups of people is funded under the National Immunisation Program and by states and territories.

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Overview

What

Diphtheria is an acute illness caused by the bacterium Corynebacterium diphtheriae. Infection can produce a thick membrane in the pharynx, causing severe respiratory obstruction. The bacteria produce a toxin that can cause life-threatening heart failure and paralysis.

Who

Diphtheria-containing vaccine is recommended for:

• routine vaccination in infants, children and adolescents
• routine booster vaccination in adults, including those in special risk groups such as
  • laboratory workers
  • travellers to countries where health services are difficult to access
• vaccination of people who have missed doses of diphtheria-containing vaccine

How

Diphtheria-containing vaccines are only available in Australia as combination vaccines that include other antigens such as pertussis and tetanus.

Diphtheria-containing vaccines are recommended for children at 2, 4, 6 and 18 months, and 4 years of age, and adolescents at 11–13 years of age.

A diphtheria-containing vaccine booster is recommended for adults at 50 years of age.

Vaccination is recommended every 10 years for travellers to countries where health services are difficult to access. Travellers to some areas where there is a higher risk of acquiring diphtheria are recommended to be vaccinated every 5 years.

Laboratory workers who may be exposed to toxigenic Corynebacterium diphtheriae in their jobs are recommended to have a serology test for diphtheria antibodies every 10 years. They should receive a booster dose of either dTpa (reduced antigen content diphtheria-tetanus-acellular pertussis) or dT (diphtheria-tetanus) if the diphtheria antitoxin level is <0.1 IU per mL.

Adolescents and adults who have never had a diphtheria-containing vaccine are recommended to receive 3 doses of diphtheria-containing vaccine with at least 4 weeks between doses, and booster doses at 10 years and 20 years after the primary course.

Why

Diphtheria is rare in Australia but remains endemic in many developing countries. Most Australian cases are imported from overseas, although an unimmunised person who had never been overseas died from diphtheria myocarditis in Queensland in 2018.

Recommendations

Infants and children

Adolescents

Adults

Adolescents and adults who have never received a diphtheria-containing vaccine

Women who are pregnant or breastfeeding

Laboratory workers who may be exposed to diphtheria in their jobs

Travellers

Vaccines, dosage and administration

Diphtheria vaccines available in Australia

The Therapeutic Goods Administration website provides product information for each vaccine.

See also Vaccine information and Variations from product information for more details.

Combination vaccines

Dose and route

The dose of all diphtheria-containing vaccines is 0.5 mL given by intramuscular injection.

Co-administration with other vaccines

Do not mix DTPa- or dTpa-containing vaccines or dT vaccine with any other vaccine in the same syringe, unless specifically registered for use in this way.

Diphtheria-containing vaccines can be co-administered with most other vaccines.

If a person needs to receive Nimenrix and a vaccine containing tetanus toxoid, co-administration of these vaccines is preferred. Giving Nimenrix after a vaccine containing tetanus toxoid may interfere with the immune response against some meningococcal serogroups. There is uncertainty about whether this reduced immune response affects clinical protection, and there are no data on the optimal interval between the vaccines. Therefore, Nimenrix should be given as scheduled, even if it is being given shortly after a vaccine containing tetanus toxoid.

If a person needs to receive Menactra and a vaccine containing diphtheria toxoid, it is preferred that either Menveo or Nimenrix is administered instead of Menactra. If the other MenACWY vaccines are unavailable, co-administration of Menactra and the vaccine containing diphtheria toxoid is preferred, rather than delaying either vaccine. Giving Menactra after a vaccine containing diphtheria toxoid may interfere with the immune response against some meningococcal serogroups. There is uncertainty about whether this reduced immune response affects clinical protection, and there are no data on the optimal interval between the vaccines. Therefore, Menactra should be given as scheduled, even if it is being given shortly after a vaccine containing diphtheria toxoid.

Contraindications and precautions

Contraindications

The only absolute contraindications to diphtheria-containing vaccines are:

• anaphylaxis after a previous dose of any diphtheria-containing vaccine
• anaphylaxis after any component of a diphtheria-containing vaccine

Precautions

People with latex allergy

The product information for ADT booster states that the tip cap of the syringe contains latex. Consider using an alternative product in people with an allergy or sensitivity to latex.

The product information for Adacel states that the tip cap of the syringe contains latex. Consider using an alternative product in people with an allergy or sensitivity to latex.

Adverse events

Mild discomfort or pain at the injection site is common after receiving diphtheria-containing vaccine. This can last for a few days. Uncommon general adverse events after receiving dT vaccine include:

• headache
• lethargy
• malaise
• myalgia
• fever

Very rare adverse events after receiving dT vaccine include:

• anaphylaxis
• urticaria
• peripheral neuropathy

Brachial neuritis may occur after receiving diphtheria-containing vaccine. This is inflammation of a nerve in the arm, causing weakness or numbness. The excess risk is approximately 0.5–1 in 100,000 doses in adults. 5,6

Specific adverse events after receiving a combination vaccine containing both diphtheria and pertussis antigens are extensive limb swelling, febrile convulsions and hypotonic-hyporesponsive episodes. See Pertussis for more details.

Combination vaccines containing both diphtheria and pertussis antigens are safe and well tolerated in adults when given as a booster dose.3,7-9 See Pertussis.

Adverse reactions to a single dose of dTpa vaccine are similar whether a person receives the vaccine shortly after, or at a longer interval after, a previous dT vaccine.10-13 See also Pertussis.

Nature of the disease

Diphtheria is an acute illness caused by toxigenic strains of Corynebacterium diphtheriae. The bacterium is gram-positive, non-spore-forming and non-capsulate.1

The bacteria produce an exotoxin that acts locally on the mucous membranes of the respiratory tract or, less commonly, on damaged skin. It produces an adherent pseudomembrane. Systemically, the toxin acts on cells of the myocardium, nervous system and adrenals.

The incubation period is 2–5 days. The disease is communicable for up to 4 weeks, but carriers may shed organisms for longer.14 Diphtheria spreads by:

• aerosol transmission
• direct contact with skin lesions
• direct contact with articles soiled by infected people

Clinical features

Diphtheria can involve almost any mucous membrane. Pharyngeal diphtheria is by far the most common form of the disease in unimmunised people. It is characterised by an inflammatory exudate that forms a greyish or green membrane in the upper respiratory tract. This can cause acute severe respiratory obstruction.

Life-threatening complications from diphtheria include myocarditis and neuritis (usually affecting motor nerves). The case-fatality rate in the past 3 decades has been up to 16%.15

Diphtheria antitoxin neutralises unbound toxin. It was first used in the 1890s. Antibiotics and antitoxin are the main treatments for diphtheria, but may not always be successful.

Active immunisation with diphtheria-containing vaccines is the only effective way to protect against diphtheria.1,14

Epidemiology

In the early 1900s, diphtheria caused more deaths in Australia than any other infectious disease. Increasing use of diphtheria vaccines since World War II has led to its virtual disappearance.16

The current epidemiology of diphtheria in Australia is similar to that in other developed countries. Between 2001 and 2013, 7 diphtheria cases were reported in Australia. Of these, 5 were imported and 2 were linked to an imported case.17

Almost all recent cases in the United Kingdom and the United States have been associated with imported infections.18

In Australia in 2011, a fatal case of pharyngeal diphtheria occurred in an unvaccinated person who was infected by a friend who acquired diphtheria in a less developed country.19 This was the 1st death from diphtheria in Australia in more than 20 years. An unvaccinated person who had never been overseas died from diphtheria myocarditis in Queensland in 2018.

Vaccine information

Diphtheria toxoid is available in Australia only in combination with tetanus toxoid. Vaccines may also include other antigens, such as pertussis, inactivated poliovirus, hepatitis B and Haemophilus influenzae type b.

The acronym DTPa, using capital letters, signifies a child formulation of diphtheria, tetanus and acellular pertussis–containing vaccine.

The acronym dTpa signifies a formulation that contains substantially less diphtheria toxoid and pertussis antigens than the child formulation. Adolescents and adults usually receive reduced antigen dTpa vaccine because they generally respond better to diphtheria toxoid and require lower doses to establish or maintain immunity.

Immunogenicity

Diphtheria vaccination stimulates the production of antibodies, also known as ‘antitoxin’, which protect against diphtheria toxin.

The vaccine antigen is prepared by treating a cell-free toxin preparation with formaldehyde. This converts it into diphtheria toxoid, which is safe.

Diphtheria toxoid is usually adsorbed onto an adjuvant to increase its immunogenicity. Adjuvants are either aluminium phosphate or aluminium hydroxide.

The circulating levels of antitoxin required for protection from diphtheria are well described:

• Levels of <0.01 IU per mL are poorly protective.
• Levels of 0.01–0.1 IU per mL are usually protective.
• Levels of >0.1 IU per mL are associated with more certain and prolonged protection.20

Studies have shown that, 1 month after the 3-dose primary vaccination series of DTPa-hepB-IPV-Hib, 97.4–100% of infants had diphtheria antitoxin levels of ≥0.1 IU per mL. After a 4th dose in the 2nd year of life, 96.8–100% of infants had antibody levels of ≥0.1 IU per mL for both diphtheria and tetanus.21,22

A study of adults with unknown vaccination history showed that, after 3 doses of either a dT or a dTpa vaccine, 99% of adults had protective antibody levels.3

Duration of immunity

Complete immunisation induces protective levels of antitoxin that last throughout childhood. But, by middle age, at least 50% of people who have not been vaccinated since childhood have levels <0.1 IU per mL.23-25 This has been confirmed in Australia by a national serosurvey.2 The clinical significance of these antibody levels with regard to protective immunity is uncertain.

A single low dose of diphtheria toxoid in a previously immunised adult induces protective levels of antitoxin within 6 weeks.26

Transporting, storing and handling vaccines

Transport according to National Vaccine Storage Guidelines: Strive for 5.27 Store at +2°C to +8°C. Do not freeze. Protect from light.

Infanrix hexa vaccine must be reconstituted. Add the entire contents of the syringe to the vial and shake until the pellet completely dissolves. Use the reconstituted vaccine as soon as practicable. If it must be stored, hold at room temperature for no more than 8 hours.

Public health management

Diphtheria is a notifiable disease in all states and territories in Australia.

Confirmed or suspected diphtheria is of considerable public health importance. It should be notified immediately to state or territory public health authorities. Contacts usually need vaccination (either primary or booster, depending on their vaccination status) and appropriate prophylactic antibiotics.28

State and territory public health authorities can advise on and coordinate:

• public health management of diphtheria, including management of cases of diphtheria and their contacts
• access to diphtheria antitoxin
• dosage of diphtheria antitoxin
• special arrangements if hypersensitivity is suspected

Variations from product information

Routine vaccination in children and adults

Infanrix

The product information for Infanrix states that this vaccine is for:

• primary immunisation of infants aged between 2 months and 12 months
• booster dose in children aged 15 months to 6 years who have previously been vaccinated against diphtheria, tetanus and pertussis

The Australian Technical Advisory Group on Immunisation (ATAGI) recommends that Infanrix may also be used for catch-up of the primary schedule or as a booster in children <10 years of age. ATAGI also recommends that the primary schedule can start at 6 weeks of age.

Infanrix hexa

The product information for Infanrix hexa states that this vaccine is for:

• primary immunisation of infants from the age of 6 weeks
• booster dose in children 18 months of age if they need boosting for all antigens

ATAGI recommends that Infanrix hexa may also be used for catch-up of the primary schedule or as a booster in children <10 years of age.

Infanrix IPV

The product information for Infanrix IPV states that this vaccine is for:

• use in a 3-dose primary schedule for immunisation of infants from the age of 6 weeks
• a single booster dose in children ≤6 years of age who have previously been vaccinated against diphtheria, tetanus, pertussis and poliomyelitis

ATAGI recommends that Infanrix IPV may also be used for catch-up of the primary schedule or as a booster in children <10 years of age.

Quadracel

The product information for Quadracel states that this vaccine is for:

• use in a 3-dose primary schedule from the age of 2 months to 12 months
• booster dose in children from 15 months to 6 years of age who have previously been vaccinated against diphtheria, tetanus, pertussis and poliomyelitis

ATAGI recommends that Quadracel may also be used for catch-up of the primary schedule or as a booster in children aged <10 years. ATAGI also recommends that the primary schedule can start at 6 weeks of age.

Tripacel

The product information for Tripacel states that this vaccine is for:

• use in a 3-dose primary schedule from the age of 2 months to 12 months
• booster dose in children from 15 months to 8 years of age who have previously been vaccinated against diphtheria, tetanus and pertussis

ATAGI recommends that Tripacel may also be used for catch-up of the primary schedule or as a booster in children aged <10 years. ATAGI also recommends that the primary schedule can start at 6 weeks of age.

Adacel and Boostrix

The product information for Adacel (reduced antigen content dTpa) states that this vaccine is for use in people aged ≥10 years for booster doses only.

The product information for Boostrix (reduced antigen content dTpa) states this vaccine is for use in people aged ≥4 years for booster doses only.

ATAGI recommends that, when an adolescent or adult receives a 3-dose primary course of diphtheria/tetanus toxoids:

• dTpa should replace the 1st dose of dT
• the 2nd and 3rd doses should be dT

If dT is not available, dTpa can be used for all 3 primary doses.

The product information for Adacel and Boostrix states that there is no recommendation about the frequency of vaccination against pertussis in adults. ATAGI recommends that adults in contact with infants and/or at increased risk from pertussis should have received the vaccine within the past 10 years.

Adacel Polio, Boostrix and Boostrix-IPV

The product information for Adacel Polio, Boostrix and Boostrix-IPV states that vaccine is for use in people aged ≥4 years for booster doses only.

ATAGI recommends that Adacel Polio, Boostrix and Boostrix-IPV should not be used in people aged <10 years, except in certain circumstances.

ADT Booster

The product information for ADT Booster states that this vaccine is for use as a booster dose only in:

• children aged ≥5 years
• adults who have previously received at least 3 doses of diphtheria and tetanus vaccines

ATAGI recommends that, where a dT vaccine is required, ADT Booster can be used for any dose. This includes for primary immunisation against diphtheria and tetanus for any person ≥10 years of age.

Vaccination during pregnancy

The product information for Adacel states that vaccinating pregnant women is not recommended unless there is a definite risk of acquiring pertussis.

The product information for Boostrix states that the vaccine may be considered during the 3rd trimester of pregnancy when the possible advantages outweigh the possible risks for the fetus.

The product information for Adacel and Boostrix states that there is no recommendation about vaccination against pertussis in subsequent pregnancies.

ATAGI recommends that pregnant women receive a dose of pertussis-containing vaccine with each pregnancy, ideally early in the 3rd trimester.

Vaccination after tetanus-containing vaccines

The product information for Adacel, Boostrix and Boostrix-IPV states that people should not receive a dTpa-containing vaccine within 5 years of a tetanus-containing vaccine.

ATAGI recommends that, if the person needs protection against pertussis, they can receive a dTpa-containing vaccine at least 4 weeks after a dT-containing vaccine.

Contraindications

The product information for all vaccines except ADT Booster states that these vaccines are contraindicated in children with either:

• encephalopathy of unknown aetiology, or
• neurologic complications occurring within 7 days after a vaccine dose

ATAGI recommends that the only contraindications are:

• anaphylaxis after a previous dose of any diphtheria-containing vaccine
• anaphylaxis after any component of a diphtheria-containing vaccine

References

1. Tiwari TS, Wharton M. Diphtheria toxoid. In: Plotkin SA, Orenstein WA, Offit PA, Edwards KM, eds. Plotkin's vaccines. 7th ed. Philadelphia, PA: Elsevier; 2018.
2. Gidding HF, Backhouse JL, Burgess MA, Gilbert GL. Immunity to diphtheria and tetanus in Australia: a national serosurvey. Medical Journal of Australia 2005;183:301-4.
3. Theeten H, Rümke H, Hoppener FJ, et al. Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines. Current Medical Research and Opinion 2007;23:2729-39.
4. Centers for Disease Control and Prevention (CDC). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women – Advisory Committee on Immunization Practices (ACIP), 2012. MMWR. Morbidity and Mortality Weekly Report 2013;62:131-5.
5. Hamati-Haddad A, Fenichel GM. Brachial neuritis following routine childhood immunization for diphtheria, tetanus, and pertussis (DTP): report of two cases and review of the literature. Pediatrics 1997;99:602-3.
6. Institute of Medicine. Stratton KR, Howe CJ, Johnston RB, Jr., eds. Adverse events associated with childhood vaccines: evidence bearing on causality. Washington, DC: National Academy Press; 1994.
7. Blatter M, Friedland LR, Weston WM, Li P, Howe B. Immunogenicity and safety of a tetanus toxoid, reduced diphtheria toxoid and three-component acellular pertussis vaccine in adults 19–64 years of age. Vaccine 2009;27:765-72.
8. Turnbull FM, Heath TC, Jalaludin BB, Burgess MA, Ramalho AC. A randomized trial of two acellular pertussis vaccines (dTpa and pa) and a licensed diphtheria-tetanus vaccine (Td) in adults. Vaccine 2000;19:628-36.
9. Pichichero ME, Rennels MB, Edwards KM, et al. Combined tetanus, diphtheria, and 5-component pertussis vaccine for use in adolescents and adults. [erratum appears in JAMA. 2005 Dec 28;294(24):3092]. JAMA 2005;293:3003-11.
10. David ST, Hemsley C, Pasquali PE, et al. Enhanced surveillance for vaccine-associated adverse events: dTap catch-up of high school students in Yukon. Canada Communicable Disease Report 2005;31:117-26.
11. Tremblay M, Grenier JL, De Serres G, et al. Adverse events after vaccination with dTap in high school students who have previously been vaccinated with d2T5. Canada Communicable Disease Report 2006;32:25-8.
12. Halperin SA, Sweet L, Baxendale D, et al. How soon after a prior tetanus-diphtheria vaccination can one give adult formulation tetanus-diphtheria-acellular pertussis vaccine? Pediatric Infectious Disease Journal 2006;25:195-200.
13. Talbot EA, Brown KH, Kirkland KB, et al. The safety of immunizing with tetanus-diphtheria-acellular pertussis vaccine (Tdap) less than 2 years following previous tetanus vaccination: experience during a mass vaccination campaign of healthcare personnel during a respiratory illness outbreak. Vaccine 2010;28:8001-7.
14. Centers for Disease Control and Prevention (CDC). Diphtheria. In: Hamborsky J, Kroger A, Wolfe C, eds. Epidemiology and prevention of vaccine-preventable diseases. 13th ed. Washington, DC: Public Health Foundation; 2015. 
15. Vitek CR, Wharton M. Diphtheria toxoid. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 5th ed. Philadelphia, PA: Saunders Elsevier; 2008.
16. Gidding HF, Burgess MA, Kempe AE. A short history of vaccination in Australia. [erratum appears in Med J Aust 2001 Mar 5;174(5):260]. Medical Journal of Australia 2001;174:37-40.
17. NNDSS Annual Report Working Group. Australia's notifiable disease status, 2014: annual report of the National Notifiable Diseases Surveillance System. Communicable Diseases Intelligence 2016;40:E48-145.
18. Gidding HF, Burgess MA, Gilbert GL. Diphtheria in Australia, recent trends and future prevention strategies. Communicable Diseases Intelligence 2000;24:165-7.
19. NNDSS Annual Report Writing Group. Australia's notifiable disease status, 2011: annual report of the National Notifiable Diseases Surveillance System Communicable Diseases Intelligence 2013;37:E313-93.
20. Sutter RW, Hardy IR, Kozlova IA, et al. Immunogenicity of tetanus-diphtheria toxoids (Td) among Ukrainian adults: implications for diphtheria control in the Newly Independent States of the former Soviet Union. Journal of Infectious Diseases 2000;181 Suppl 1:S197-202.
21. Tichmann-Schumann I, Soemantri P, Behre U, et al. Immunogenicity and reactogenicity of four doses of diphtheria-tetanus-three-component acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b vaccine coadministered with 7-valent pneumococcal conjugate vaccine. Pediatric Infectious Disease Journal 2005;24:70-7.
22. Tregnaghi M, Zambrano B, Santos-Lima E. Antibody persistence after a primary series of a new DTaP-IPV-Hep B-PRP-T combined vaccine or separate DTaP-IPV//PRP-T and hepatitis B vaccines at 2, 4, and 6 months of age and the effect of a subsequent DTaP-IPV//PRP-T booster vaccination at 18 months of age in healthy Argentinean infants. Pediatric Infectious Disease Journal 2012;31:e24-30.
23. Hasselhorn HM, Nübling M, Tiller FW, Hofmann F. Factors influencing immunity against diphtheria in adults. Vaccine 1998;16:70-5.
24. Maple PA, Jones CS, Wall EC, et al. Immunity to diphtheria and tetanus in England and Wales. Vaccine 2000;19:167-73.
25. McQuillan GM, Kruszon-Moran D, Deforest A, Chu SY, Wharton M. Serologic immunity to diphtheria and tetanus in the United States. Annals of Internal Medicine 2002;136:660-6.
26. Marlovits S, Stocker R, Efstratiou A, et al. Effect on diphtheria immunity of combined tetanus and diphtheria booster vaccination in adults. European Journal of Clinical Microbiology and Infectious Diseases 2000;19:506-13.
27. National Vaccine Storage Guidelines: Strive for 5. 3rd ed. Canberra: Australian Government Department of Health and Ageing; 2019. https://www.health.gov.au/resources/publications/national-vaccine-storage-guidelines-strive-for-5
28. Bonnet JM, Begg NT. Control of diphtheria: guidance for consultants in communicable disease control. Communicable Disease and Public Health 1999;2:242-9.

Related vaccines

Adacel

Adacel Polio

ADT Booster

Boostrix

Boostrix-IPV

Hexaxim

Infanrix

Infanrix hexa

Infanrix IPV

Quadracel

Tripacel

Page history

Last updated

8 March 2022

Last reviewed

8 March 2022