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given in repeated doses as the tissue reaction to a dose which it was
anticipated would be sufficient to produce immunity was too severe
and the practice was evolved of giving three doses at weekly
intervals. Controlled work showed that better results could be
obtained where the intervals between the injections were rather
longer than one week. Three weekly doses preceded by a Schick test
entailed the attendance of the patient over a period of one month;
with longer intervals between injections, the period was lengthened.
To overcome the necessity for repeated inoculations an attempt was
made to so alter the antigen that after injection it was liberated
into the body tissues only slowly—the so-called "depot" effect—
the hope being that the gradual release of a single dose of antigen
into the tissues would effect the same results as the repeated inoculations.
The immobilising of the antigen was to be brought about
by the tissue re-action to alum added to the preparation, so there
was marketed alum-precipitated toxoid, a preparation advertised
as the one-shot dose antigen. A number of satisfactory accounts
were published from which it appeared that in some districts this
preparation effected a conversion rate comparable to that obtained
by the use of other preparations, but subsequent results have not
justified the optimistic claims made in the early days. The efficacy
of an antigen to change a Schick positive into a negative re-actor
depends on factors independent of the quality of the preparation,
its dosage and interval between injections, the chief perhaps being
the state of the tissues of the individual who is being injected.
This depends very largely on his history of contact with the
diphtheria organism. In those areas where diphtheria is constantly
smouldering, young children have been subjected to repeated subinfective
doses and even those who are not immune as disclosed
by the Schick test may be bordering on the state of immunity.
In such a case even a small dose of any preparation is sufficient to
tip the scale and render the child Schick negative. Very different,
however, is the case of a child who has not been exposed to these
repeated sub-infective doses of the diphtheria organism. In such
a child the body tissues have not been stimulated to produce the
necessary anti-toxin and in such cases even three injections of a
potent antigen may be insufficient to raise the anti-toxic content
of the blood serum to a degree sufficient to give a Schick negative
re-action, and a child may still re-act positively after three doses.
This accounts for those children who need additional doses after a
complete course. In this district the average level of immunity
must be low. No child under ten primarily Schick tested has given
a negative result, and most of those even up to the age of thirteen
have been found to be positive. For this reason no modifications
of the original proposals have since been made as it seemed that
only those methods which have been proved to be most successful
can be recommended for use in a district where the general level of
the immunity must be low. The use of the one-shot method is
being gradually abandoned, though the same preparation is now