Introduction

Diphtheria Vaccine (Toxoid)

INTRODUCTION
Diphtheria is an acute communicable respiratory infection caused by Corynebacterium diphtheriae. Vaccination confers protection against disease by production of antitoxins to the diphtheria toxin. When treated with formaldehyde and heat, diphtheria toxin loses its ability to bind to cells and its enzymatic activity (toxigenicity), but retains its immunogenicity. This treatment converts diphtheria toxin into a toxoid. Then, the vaccine is produced from purified inactivated toxin from a toxigenic strain of Corynebacterium diphtheriae.

AVAILABLE VACCINES
The vaccine is made from a cell-free purified toxin extracted from a strain of C. diphtheriae. This is treated with formaldehyde, which converts it into diphtheria toxoid. This is adsorbed on to an adjuvant - either aluminium phosphate or aluminium hydroxide - to improve its immunogenicity. Diphtheria vaccines are available in 2 strengths according to dose of toxoid: o High-dose: vaccines contain >30 IU of diphtheria toxoid and are used to achieve satisfactory primary immunization of children as in DTaP vaccine (capital D = high-dose). o Low-dose: vaccines contain 2 IU of toxoid and are used for primary immunization of those aged over 10 years and for subsequent boosters as in dTaP (lower case d = lowdose). Monovalent diphtheria vaccine is not available. Vaccination should only be given as a component of the following combination products: o Diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenzae type b vaccines (DTaP/IPV/Hib). o Diphtheria, tetanus, acellular pertussis and inactivated polio vaccines (DTaP/IPV or dTaP/IPV). o Tetanus, diphtheria and inactivated polio (Td/IPV). The above vaccines are thiomersal-free. They are inactivated, do not contain live organisms and cannot cause the diseases against which they protect. Td/IPV vaccine should be used where protection is required against tetanus, diphtheria or polio in order to provide comprehensive long-term protection against all three diseases. Diphtheria Vaccine

Storage

STORAGE
Vaccines should be stored in the original packaging at +2C to +8C and protected from light. All vaccines are sensitive to some extent to heat and cold. Heat speeds up the decline in potency of most vaccines, thus reducing their shelf life. Effectiveness cannot be guaranteed for vaccines unless they have been stored at the correct temperature. Freezing may cause increased reactogenicity and loss of potency for some vaccines. It can also cause hairline cracks in the container, leading to contamination of the contents.

PRESENTATION
Diphtheria vaccine is only available as part of combined products. It is supplied as a cloudy white suspension, either in a single dose ampoule or pre-filled syringe. The suspension may settle during storage, so the vaccine should be shaken to distribute the suspension uniformly before administration.

ADMINISTRATION
Site:
o Five doses of a diphtheria-containing vaccine are given intramuscularly. o Upper arm or anterolateral thigh sites are recommended to minimize risks of local reactions. o Other vaccinations such as measles, mumps and rubella (MMR), meningitis C or hepatitis B can be given at the same time but should be injected at an alternative site and preferably in a different limb.

Schedule:
Primary Immunization: o All infants should receive the primary immunization course involving 3 doses (0.5ml) of diphtheria-containing vaccine. o It is recommended that DTaP/IPV/Hib be given at 2, 4 and 6 months of age as levels of passively acquired maternal antitoxin decline. o If necessary, the same dosing schedule can be used in children up to 10 years of age. o Older individuals should receive 3 doses of a d-containing preparation (usually Td/IPV) at monthly intervals.

Diphtheria Vaccine

The duration of protection: Booster Doses: The first booster dose (0.5ml) is given to children between the ages of 18-24 months: o Either DTaP/IPV or dTaP/IPV will elicit an adequate immune response. o If primary immunization has been delayed, the first booster dose must be given at least one year after completion of the initial course. o All individuals aged over 10 years who require a first booster should be given a dose of Td/IPV. The second booster (0.5ml) dose is offered to 4-6 year olds by the school health service: o The Td/IPV preparation should always be used. o If previous doses have been delayed, the second booster should be given at least 5 years after the first booster. o Note that patients may have inadvertently already received a diphtheria booster associated with tetanus toxoid. Adults with an incomplete primary series may also benefit from a booster dose, if long-term protection is required. A second booster dose raises immunity to 92%.

Other Recipients:
Travelers: Travelers to endemic areas should be fully immunized before travel. Travelers to developing countries for over one month's duration, who had their last diphtheria booster dose more than 10 years ago, should be offered a further booster of Td/IPV. Laboratory and Healthcare Workers: Individuals who may be exposed to diphtheria at work must be fully immunized and should be offered a booster dose. Further boosters should be given every 10 years if risks persist. Workers who are unimmunized should undergo the complete vaccination schedule with subsequent antibody testing as proof of immunity. Contacts: Close contacts of a diphtheria case should be offered full immunization or a booster if their most recent vaccine dose was more than 12 months ago.

THE DURATION OF PROTECTION:

It is between five to ten years. This covers childhood, which is the time of greatest exposure and greatest risk of death from diphtheria.

Diphtheria Vaccine

Effectiveness of the vaccine:

EFFECTIVENESS OF THE VACCINE:

After a properly spaced primary series of DTaP or Tdap, approximately 95% of people will have protective levels of diphtheria antitoxin and 100% will have protective levels of tetanus antitoxin in their blood. However, antitoxin levels decrease with time so routine boosters with tetanus and diphtheria toxoids are recommended every 10 years.

ADVERSE REACTIONS
Mild Adverse Reactions (Common):
o Fever (up to about 1 child in 4). o Redness or swelling where the shot was given (up to about 1 child in 4). o Soreness or tenderness where the shot was given (up to about 1 child in 4). These problems occur more often after the 4th and 5th doses of the DTaP series than after earlier doses. Sometimes the 4th or 5th dose of DTaP vaccine is followed by swelling of the entire arm or leg in which the shot was given, lasting 1-7 days (up to about 1 child in 30). o Fussiness or easy upset (up to about 1 child in 3). o Tiredness or poor appetite (up to about 1 child in 10). o Vomiting (up to about 1 child in 50). These problems generally occur 1-3 days after the shot.

Moderate Adverse Reactions (Uncommon):

o Seizure (jerking or staring) (about 1 child out of 14,000). o Non-stop crying, for 3 hours or more (up to about 1 child out of 1,000). o High fever, over 105oF (about 1 child out of 16,000).

Severe Adverse Reactions (Very Rare):

o Serious allergic reaction (less than 1 out of a million doses). o Long-term seizures, coma, or lowered consciousness. o Permanent brain damage. These are so rare it is hard to tell if they are caused by the vaccine.

Diphtheria Vaccine

Contraindications

CONTRAINDICATIONS
Absolute Contraindication:
o o o o Confirmed anaphylactic reaction to diphtheria toxoid-containing vaccine. Confirmed anaphylactic reaction to neomycin, streptomycin or polymyxin B. Acute illness with systemic upset and fever. Evolving or undiagnosed, deteriorating neurological abnormalities.

Relative Contraindication:
o History of a stable neurological condition, seizures or febrile convulsions (without neurological deterioration). o Fever, persistent screaming, severe local reactions or hypotonic-hyporesponsive episodes following previous diphtheria vaccinations. o Immunosuppression including HIV infection. o Pregnancy or breast-feeding.

REFERENCES
o The Green Book: Immunization against infectious diseases. o The Immunological Basis for Immunization, Module 2: Diphtheria, World Health Organization. o Guidance for consultants in communicable disease control: control of diphtheria. o The Yellow Book: Health information for overseas travel.

DONE BY Dr. Mahmoud Ahmed Mahmoud Alexandria University of Medicine

Diphtheria Vaccine