s 15.1 Introduction
s 15.1.1 Diphtheria is an acute infectious disease affecting the upper
respiratory tract and occasionally the skin. It is characterised by an
inflammatory exudate which forms a greyish membrane in the
respiratory tract which may cause respiratory obstruction. The
incubation period is from two to five days. Patients with disease may be
infectious for up to four weeks, but carriers may shed Corynebacteria
diphtheriae for longer. A toxin is produced by diphtheria bacilli which
affects particularly myocardium and nervous and adrenal tissues. Spread
is by droplet infection and through contact with articles soiled by
infected persons (fomites). In countries where hygiene is poor, cutaneous
diphtheria is the predominant source of infection.
s 15.1.2 Effective protection against the disease is provided by active
immunisation. The introduction of immunisation against diphtheria on
a national scale in 1940 resulted in a dramatic fall in the number of
notified cases and deaths from the disease. In 1940, 46,281 cases with
2,480 deaths were notified, compared with 37 cases and six deaths in
1957. From 1986 to 1995, 38 isolates of toxigenic C. diphtheriae were
identified by the PHLS Diphtheria Reference Unit. Of these, 19 were
carriers and 7 were cutaneous infections. There was one death in 1994:
a 14 year old with no record of immunisation who had visited Pakistan.
Immunisation against Infectious Disease 67
Notifications of diptheria to ONS
England and Wales (1940-1995)
Immunisation against Infectious Disease
1940 1950 1960 1970 1980 1990
s 15.1.3 The increase in notifications of diphtheria since 1992 has
been due to a rise in isolations of a non-toxigenic C. diphtheriae var
gravis. Presentation is usually with a sore throat without signs of
s 15.1.4 Since 1991, there has been an epidemic of diphtheria in
Russia, now involving other Newly Independent States of the former
Soviet Union. In 1995, approximately 52,000 cases of diphtheria and
1,700 deaths were reported. The causes of this epidemic are low
immunisation coverage in young children, waning immunity in adults
and large scale population movements. There have been some
importations from the former Soviet Union countries into neighbouring
countries but no evidence of importation into the UK.
s 15.1.5 The disease and the organism have been virtually eliminated
from the United Kingdom; the few cases which have occurred in recent
years have nearly all been imported from the Indian subcontinent or
from Africa, with minimal spread. There is thus no possibility now of
acquiring natural immunisation from sub-clinical infection. High
immunisation uptake must be maintained in order to protect the
population against the possibility of a resurgence of the disease which
could follow the introduction of cases or carriers of toxigenic strains
s 15.1.6 Recent published data indicate that approximately 38% of
UK blood donors are susceptible to diphtheria. A significant trend of
decreasing immunity with increasing age was apparent: 25% of donors
aged 20-29 were susceptible compared with 53% of those aged 50-59.
s 15.2 Diphtheria vaccine
s 15.2.1 Diphtheria immunisation protects by stimulating the
production of antitoxin which provides immunity to the effects of the
toxin. The immunogen is prepared by treating a cell-free purified
preparation of toxin with formaldehyde, thereby converting it into the
innocuous diphtheria toxoid. This however is a relatively poor
immunogen, and for use as a vaccine it is usually adsorbed on to an
adjuvant, either aluminium phosphate or aluminium hydroxide.
Bordetella pertussis also acts as an effective adjuvant.
Immunisation against Infectious Disease 69
s 15.2.2 The recommended vaccines for immunisation are:
Adsorbed diphtheria/tetanus/pertussis (DTP).
Adsorbed diphtheria/tetanus (DT).
Adsorbed diphtheria (D).
Adsorbed low dose diphtheria vaccine for adults (d).
Adsorbed tetanus/low dose diphtheria vaccine for adults (Td).
The dose is 0.5ml given by intramuscular or deep subcutaneous
Plain vaccines are less immunogenic and have no advantage in terms of
reaction rates and are no longer available.
Vaccines should be stored at 2-8°C and protected from light. Vaccine
which has been frozen should not be used. Disposal should be by
incineration at a temperature not less than 1100°C at a registered waste
s 15.3 Recommendations
s 15.3.1 For immunisation of infants and children up to ten years of
a. Primary immunisation
Diphtheria vaccine as a component of triple vaccine (diphtheria toxoid,
tetanus toxoid and Bordetella pertussis toxoid) is recommended for
infants from two months of age. Adsorbed vaccine should be used as it
has been shown to cause fewer reactions than plain vaccine which is no
longer available. If the pertussis component is contraindicated,
adsorbed diphtheria/tetanus vaccine should be used. A course of
primary immunisation consists of three doses starting at two months
with an interval of one month between each dose (see 11.1). If a course
is interrupted it may be resumed; there is no need to start again.
b. Reinforcing immunisation
Booster doses of vaccine containing diphtheria and tetanus toxoids are
recommended for: (i) children before school entry - DT, preferably at
least three years after the last dose of the primary course, and (ii) before
leaving school at 13 to 18 years of age - Td, both at the same time as
70 Immunisation against Infectious Disease
In approximately 25% of children, a fifth tetanus vaccine dose is said to
have been given by the time the school leaving booster (Td) is due. If a
child requires a tetanus booster after a tetanus prone wound, after the
fourth dose has been given (at around 4 years of age) and ten years has
elapsed, then Td should be given. The school leaving Td dose is then not
If there is a documented history of a fifth dose of tetanus vaccine having
already been given when the school leaving booster is due, and supplies
of a low dose diphtheria vaccine product are readily available (either low
dose diphtheria vaccine (d) or 0.1 ml of paediatric strength diphtheria
vaccine (D)), then one of these latter two products should be used. If
neither is available, then Td should be given with an interval of at least
one month since the last dose of tetanus vaccine. Recent experience has
shown that when Td is given to children who have already had 5 doses
of tetanus vaccine, there is some increase in the number who have local
reactions and low grade pyrexias, but no increase in the numbers with
pyrexias over 38.5°C
s 15.3.2 Immunisation of persons aged ten years or over
a. Primary immunisation
Low dose diphtheria vaccine for adults (d) must be used because of the
possibility of a reaction in an individual who is already immune. Past
experience showed that when full strength diphtheria vaccine
preparations (D) were given to adults, there were considerably more
localised and generalised reactions, such as high fever. Three doses
(0.5ml) of low dose vaccine for adults (d) should be given by deep
subcutaneous or intramuscular injection at intervals of one month. When
this product is not available, then a 0.1 ml injection of the standard
paediatric diphtheria vaccine (D) may be given as an alternative. For
adults who have never received either diphtheria or tetanus vaccine
previously, three doses of Td should be used, each given one month apart.
b. Reinforcing immunisation
A single dose of 0.5ml of low-dose diphtheria vaccine (d) must be used
for all persons aged ten years and over. When this product is not
available, then a 0.1 ml injection of the standard paediatric diphtheria
vaccine (D) may be given as an alternative. When a reinforcing dose of
tetanus vaccine is also required, then Td should be used. Prior Schick
testing is not necessary and the material is no longer available.
Immunisation against Infectious Disease 71
s 15.3.3 Children given DTP at monthly intervals without a booster
dose at 18 months have been shown to have adequate levels of
diphtheria and tetanus antibody at school entry. A booster dose at 18
months for such children is therefore not necessary.
s 15.3.4 Travel: Primary or reinforcing doses are recommended for
travellers to epidemic or endemic areas (see ‘Health Information for
Overseas Travel’ for more information).
s 15.3.5 Contacts of a diphtheria case, or carriers of a toxigenic strain
Individuals exposed to such a risk should be given a complete course or
a reinforcing dose according to their age and immunisation history as
a. Immunised children up to ten years.
One injection of diphtheria vaccine (D).
b. Immunised children ten years and over, and adults.
One injection of low dose diphtheria vaccine for adults (d or Td).
c. Unimmunised children under ten years.
Three injections of diphtheria (D) vaccine (or DTP and polio vaccines if
appropriate) at monthly intervals.
d. Unimmunised children ten years and over, and adults.
Three injections of low dose diphtheria vaccine for adults (d) or Td at
Unimmunised contacts of a case of diphtheria should in addition be
given a prophylactic course of erythromycin or penicillin. Symptomatic
contacts (including close contacts) of cases of sore throat associated with
non-toxigenic C. diphtheriae should be swabbed and treated
accordingly; asymptomatic contacts do not require swabbing or
antibiotic prophylaxis. Contacts of cases of C. ulcerans do not require
prophylaxis as human to human transmission does not occur.
s 15.3.6 HIV positive individuals may be immunised against
diphtheria in the absence of any contraindications.
72 Immunisation against Infectious Disease
s 15.4 Testing for diphtheria immunity
The material for carrying out the Schick test is no longer available. Individuals
who may be exposed to diphtheria in the course of their work should have
their immunity checked by antibody testing at least three months after
immunisation is completed and boosted at ten year intervals thereafter.
s 15.5 Adverse reactions
s 15.5.1 Swelling and redness at the injection site are common.
Malaise, transient fever and headache may also occur. A small painless
nodule may form at the injection site but usually disappears without
sequelae. Severe anaphylactic reactions are rare. Neurological reactions
have been reported occasionally.
s 15.5.2 Severe reactions should be reported to the Committee on
Safety of Medicines using the yellow card system.
s 15.6 Contraindications
s 15.6.1 a. If a child is suffering from any acute illness, immunisation
should be postponed until the child has fully recovered. Minor
infections without fever or systemic upset are not reasons to postpone
b. Immunisation should not proceed in children who have had a severe
local or general reaction to a preceding dose (see 7.2.2), if it is thought
that the diphtheria component has caused the preceding reaction.
Reactions to the pertussis component of DTP are the most likely and
immunisation should proceed with DT; acellular pertussis vaccine can be
used if the previous reaction was a local one.
s 15.6.2 When there is a need to control an outbreak, diphtheria
vaccine may have to be given to individuals suffering from acute febrile
illness. Low-dose diphtheria vaccine for adults (d or Td) must be used
for persons aged ten years and over.
Immunisation against Infectious Disease 73
s 15.7 Diphtheria antitoxin
Diphtheria antitoxin is now only used in suspected cases of diphtheria. Tests
with a trial dose to exclude hypersensitivity should precede its use. It should
be given without waiting for bacteriological confirmation since its action is
specific for diphtheria. It may be given intramuscularly or intravenously, the
dosage depending on the clinical condition of the patient. This is shown in the
following table. It is no longer used for diphtheria prophylaxis because of the
risk of provoking a hypersensitivity reaction to the horse serum from which it
is derived. Unimmunised contacts of a case of diphtheria should be promptly
investigated, kept under surveillance and given antibiotic prophylaxis and
vaccine, as in 15.3.5.
Table: Dosage of antitoxin recommended for various types of
Type of diphtheria Dosage (units) Route
Nasal 10,000 - 20,000 Intramuscular
Tonsillar 15,000 - 25,000 Intramuscular or
Pharyngeal or laryngeal 20,000 - 40,000 Intramuscular or
Combined types or 40,000 - 60,000 Intravenous
Severe diphtheria 40,000 - 100,000 Intravenous or part
e.g. with extensive intravenous and part
membrane and/or severe intramuscular
If acute anaphylaxis develops, intravenous adrenaline (0.2 to 0.5ml of 1:1000
solution) should be administered immediately by intravenous injection.
74 Immunisation against Infectious Disease
Antitoxin is probably of no value for cutaneous disease, although some
authorities use 20,000 to 40,000 units of antitoxin because toxic sequelae
have been reported.
s 15.8 Supplies
s 15.8.1 Adsorbed diphtheria/tetanus/pertussis (DTP) and adsorbed
diphtheria/tetanus (DT) vaccines (15.2.2) are manufactured by Evans
Medical (Tel. 01372 364000) and Pasteur Merieux MSD Ltd (Tel. 01628
773200). Adsorbed diphtheria vaccine is manufactured by Evans
s 15.8.2 Low-dose diphtheria vaccine for adults (d) is manufactured
by Swiss Serum and Vaccine Institute, Berne, and distributed in the UK
by Farillon (Tel. 01708 379000).
s 15.8.3 Adsorbed low dose diphtheria vaccine for adults combined
with tetanus (Td) is manufactured by Pasteur Merieux MSD Ltd (Tel.
s 15.8.4 These vaccines are supplied by Farillon (Tel. 01708 379000)
as part of the childhood immunisation programme, except for the
syringe presentation of adsorbed low dose diphtheria vaccine for adults
combined with tetanus (Td) which is supplied by Pasteur Merieux MSD
Ltd (Tel. 01628 773200).
s 15.8.5 In Scotland these vaccines can be obtained through Scottish
Healthcare Supplies Division of Common Service Agency (Tel. 0131 552
s 15.8.6 Diphtheria antitoxin is supplied in vials containing 1000 iu
per ml. Manufactured by Pasteur Merieux MSD Ltd and distributed in
the UK by the Communicable Disease Surveillance Centre (Tel 0181 200
6868). In Northern Ireland the source of diphtheria antitoxin is the
Public Health Laboratory, Belfast City Hospital, Lisburn Road, Belfast
Tel. 01232 329241.
Immunisation against Infectious Disease 75
s 15.9 Bibliography
Immunity of children to diphtheria, tetanus and poliomyelitis.
Bainton D, Freeman M, Magrath D, Sheffield F W, Smith J G W.
BMJ 1979; (1), 854-857.
Advantages of aluminium hydroxide adsorbed combined diphtheria, tetanus
and pertussis vaccines for the immunisation of infants.
Butler N R, Voyce M A, Burland W M, Hilton M L.
BMJ 1959; (1), 663-666.
Susceptibility to diphtheria.
Report of Ad Hoc Working Group.
Lancet 1978; (i), 428-430.
Immunisation of adults against diphtheria.
Sheffield F W, Ironside A G, Abbott J D.
BMJ 1978; (2), 249-250.
Durability of immunity to diphtheria, tetanus and poliomyelitis after a three
dose immunisation schedule completed in the first eight months of life.
Jones E A, Johns A, Magrath D I, Melville-Smith M, Sheffield F.
Vaccine 1989: 7; 300-2.
Enhanced surveillance of non-toxigenic C.diphtheriae infections, CDR Weekly
Report 1996; 6(4);29.
Manual for the management and control of diphtheria in the European Region
Copenhagen: The Expanded Programme on Immunisation in the European
Region of WHO, 1994.
Diphtheria: Manual for the Laboratory diagnosis of Diphtheria
Copenhagen : The Expanded Programme on Immunisation in the European
Region of WHO, 1994.
Diphtheria Immunity in UK Blood Donors
Maple P A, Efstratiou A, George R C et al
Lancet 1995; 345 : 963-65
76 Immunisation against Infectious Disease