Content
Available Vaccines
Diphtheria
In this chapter:
Introduction
Diphtheria is an acute, communicable respiratory infection caused by Corynebacterium diphtheriae. The causative organism produces a toxin that results in local tissue destruction and produces membranous inflammation of the upper respiratory tract. The organism itself is rarely invasive, but a potent exotoxin produced by some strains (toxigenic strains) causes tissue damage through local and systemic actions. The toxin may then undergo haematogenous dissemination resulting in myocarditis and neuritis. Pharyngeal diphtheria, the commonest form of the disease can cause acute severe respiratory obstruction.
The disease is spread by transmission of respiratory tract droplet or by direct contact with skin lesions or articles soiled by infected persons. Humans are the only known reservoir of Corynebacterium diphtheriae and the disease is usually spread by close personal contact with a case or carrier. Carriers are important in disease transmission as natural or vaccine induced immunity does not prevent carriage.
In Malaysia, the incidence of the disease has declined dramatically with the introduction of routine childhood immunisation and improved living standards. The incidence rate of diphtheria has been sustained to less than 1 per 100,000 population for the past 20 years. There were no cases reported in 2011 and 2012. However, the disease started to re-emerge in 2013 and has shown a dramatic increase in 2016 and 2017 with 31 and 32 cases reported in the respective years. In 2018, the number of cases reported was 18 with an incidence rate of 0.05 per 100,000 population.
Although childhood vaccination coverage is important to produce herd immunity, it is known that immunity acquired from childhood vaccination wanes in the absence of boosters later in life, and older adults might not be adequately protected. It has been shown that only 60% of the overall population sample had immunity to diphtheria (defined as an anti-diphtheria toxoid concentration of >0.1 IU/mL). This immunity declined progressively with increasing age from 91% at age 6–11 years and 80% among adolescents aged 12–19 years, to approximately 30% among those aged 60–69 years.
Vaccines
- This is a toxoid-derived vaccine that is adsorbed onto an adjuvant (aluminium salt, usually aluminium phosphate) to increase its immunogenicity.
- Diphtheria toxoid is only available as a component of combination vaccines. The diphtheria vaccine is present in combination with tetanus toxoid (DT, Td) or with both tetanus toxoid and pertussis (DTaP/Tdap).
- Other combinations available include DTaP-HepB-Hib-IPV and DTaP-IPV/Hib which are mainly used in childhood immunisation.
Note:
Upper-case letters in the above abbreviations denote full-strength doses of diphtheria (D) and tetanus (T) toxoids and pertussis (P) vaccine. Lower-case “d” and “p” denote reduced doses of diphtheria and pertussis used in the adolescent/adult formulations. The “a” in DTaP and Tdap stands for “acellular”, meaning that the pertussis component contains only a part of the pertussis organism.
Vaccines Available in Malaysia
- Adacel® (Tdap; tetanus-diphtheria-acellular pertussis)
Sanofi Pasteur (M) Sdn Bhd/Sanofi Pasteur Limited, Canada - Adacel® Polio (Tdap -IPV; tetanus-diphtheria-acellular pertussis-inactivated polio)
Sanofi Aventis (M) Sdn Bhd/Sanofi Pasteur - Boostrix® (Tdap; tetanus-diphtheria-acellular pertussi)
GlaxoSmithKline Pharmaceuticals (M) Sdn Bhd/GlaxoSmithKline Biologicals S.A., Belgium - Boostrix-Polio® (Tdap-IPV; tetanus-diphtheria-acellular pertussis-inactivated polio)
GlaxoSmithKline Pharmaceuticals (M) Sdn Bhd / GlaxoSmithKline Biologicals S.A.,Belgium - Infanrix Hexa® (DTaP; diphtheria-tetanus-acellular pertussis inactivated polio-Hib-Hep B)
GlaxoSmithKline Pharmaceutical Sdn Bhd/GlaxoSmithKline Biologicals S.A., Belgium - Infanrix-IPV+Hib® (DTaP; diphtheria-tetanus-acellular pertussis-inactivated polio-Hib)
GlaxoSmithKline Pharmaceutical Sdn Bhd/GlaxoSmithKline Biologicals S.A., Belgium - Infanrix-IPV® (DTaP; diphtheria-tetanus-acellular pertussis-inactivated polio) GlaxoSmithKline Pharmaceutical Sdn Bhd/GlaxoSmithKline Biologicals S.A., Belgium
- Adsorbed DT (DT; diphtheria- tetanus)
Propharm (M) Sdn Bhd/FT Bio Farma, Indonesia - DTP (DTP; diphtheria-tetanus-acellular pertussis)
Propharm (M) Sdn Bhd/FT Bio Farma, Indonesia - Pentaxim® (DTaP; diphtheria-tetanus-acellular pertussis-inactivated polio/Hib)
Sanofi-Aventis (M) Sdn Bhd/Sanofi Pasteur, France - Hexaxim® (DTaP; diphtheria-tetanus-acellular pertussis-inactivated polio-Hib-Hep B)
Sanofi-Aventis (M) Sdn Bhd/Sanofi Pasteur, France - SII Diphtheria and Tetanus Vaccine Adsorbed (Paediatric) – 10 and 20 doses (DT; diphtheria-tetanus)
SM Pharmaceuticals Sdn Bhd/Serum Institute of India - SII Diphtheria, Tetanus and Pertussis Vaccine Adsorbed- 10 and 20 doses (DTaP; diphtheria-tetanus-acellular pertussis)
SM Pharmaceuticals Sdn Bhd/Serum Institute of India
Mode of Administration
The dose is 0.5mL given by intramuscular (IM) injection.
Co-administration with Other Vaccines
Several vaccines can be given together as long as there are no contraindications for individual agents. There are no contraindications to simultaneous administration of live attenuated vaccines with inactivated or toxoid vaccines. Do not mix Tdap or Td vaccines with other vaccines in the same syringe unless approved for mixing by the manufacturer.
Contraindications and Adverse Effects
The only absolute contraindication to diphtheria containing vaccine is anaphylaxis reaction after the previous dose or to any component of the vaccine.
Adverse effects reported include pain, tenderness, localised erythema and oedema at the injection site. Fever, headache, lethargy and myalgia are rare.
To date the most frequently reported adverse events for diphtheria containing vaccines in children received by the National Pharmaceutical Regulatory Agency (NPRA) include injection site reactions such as injection site erythema, fever and rash. Cases of febrile seizures and convulsions have also been reported in children.
Target Group in Malaysia
- All adults lacking a completed primary series of diphtheria and tetanus toxoids should complete the series with Tdap/Td.
- All adults for whom 10 years or more have elapsed since completion of their primary series, or since their last booster dose, should receive a dose of Tdap. Thereafter, a booster dose of Td should be administered every 10 years. There is no need to repeat doses if the schedule for the primary series or booster doses is delayed. For those in contact with small children, Tdap as the 1st dose may be more appropriate to prevent the transmission of pertussis. Subsequent booster doses of Td every 10 years can then be given.
- Patients who have recovered from diphtheria should complete the full immunisation schedule as the disease does not confer immunity.
- All household and other close contacts who have received less than 3 doses of diphtheria toxoid or whose vaccination status is unknown, should receive an immediate dose of a diphtheria toxoid containing preparation and should complete the primary series according to schedule. Close contacts who have completed a primary series of 3 doses or more and, who have not been vaccinated with diphtheria toxoid within the previous 5 years, should receive a booster dose of a diphtheria toxoid-containing preparation appropriate for their age.
Implications for Healthcare Workers (HCWs)
Regardless of age, all HCWs should receive a single dose of Tdap, as soon as feasible, if they have not previously received it. Tdap can be administered regardless of interval since the last tetanus or diphtheria containing vaccine. Td boosters are advocated every 10 years thereafter.
Evidence for Effectiveness
Complete immunisation induces protective levels of diphtheria antitoxin which lasts throughout childhood. However, by middle age, at least 50% of persons not vaccinated since childhood have antitoxin levels <0.1IU/ml. A level >0.1IU/ml is required to provide definite and prolonged protection. The administration of a single dose of toxoid in previously immunised adults would be able to induce protective levels within 6 weeks.
Recommendations for Vaccination for Pertussis, Tetanus, and Diphtheria
- Primary vaccination in adults: Three doses of vaccine are required with an interval of 4-6 weeks between the 1st and 2nd doses, and 6-12 months between the 2nd and 3rd doses. Tdap can be used for the 1st dose with Td vaccine for the subsequent doses.
- Booster vaccination: Persons aged ≥19 years who previously have not received a dose of Tdap should receive a single dose of Tdap. To ensure continued protection against tetanus and diphtheria, booster doses of Td should be administered every 10 years throughout life.
- Do NOT administer DTaP to adolescents and adults as the higher doses of the diphtheria and pertussis components may result in greater adverse effects.
References
- Centers for Disease Control and Prevention (CDC). (2011). Recommendations of the Advisory Committee on Immunisation Practices (ACIP). Immunisation of Health-Care Personnel, MMWR, 60(RR07), 1-45. https://www.cdc.gov/mmwr/pdf/rr/rr6007.pdf
- Centers for Disease Control and Prevention (CDC). (2018). Recommendations of the Advisory Committee on Immunization Practices. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: MMWR, 67(2), 1-44 https://www.cdc.gov/mmwr/volumes/67/rr/rr6702a1.htm
- Malaysian National Centre of Adverse Drug Reactions database. https://npra.gov.my/
- Marlovit, S., Stocker,R., Efstratiou, A., et al. (2000). Effect on diphtheria immunity of combined tetanus and diphtheria booster vaccination in adults. Eur J Clin Microbiol Infect Dis, 19, 506-13
- McQuillan, G.M., Kruszon-Moran, D., Deforest, A., Chu, S.Y., Wharton, M. (2002). Serologic immunity to diphtheria and tetanus in the United States. Ann Intern Med, 136, 660-6
- Ministry of Health of Malaysia (MOH). (2011-2019). Health facts: Incidence rate and mortality rate of communicable diseases. https://www.moh.gov.my/index.php/pages/view/58
- Mohd Khalid, M.K.N., Ahmad, N., Fen Hii, S. Y., Abd Wahab, M.A., Hashim, R., Liow, Y.L. (2018). Molecular characterization of Corynebacterium diphtheriae isolates in Malaysia between 1981 and 2016. Journal of Medical Microbiology, 68, 105-110. https://doi.org/10.1099/jmm.0.000881
- Ministry of Health Malaysia. (2019). National Pharmaceutical Control Bureau (NPCB). Senarai Produk Vaksin Berdaftar Dengan Pihak Berkuasa Kawalan Dadah
- Sutter, R.W., Hardy, I.R., Kozlova, I.A., et al. (2000). Immunogenicity of tetanus-diphtheria toxoids (Td) among Ukrainian adults: Implications for diphtheria control in the Newly Independent States of the former Soviet Union. J Infect Dis, 181 Suppl 1, S197-202 60(RR07): 1-45