033 - Immunization with Diphtheria Toxoid (Anatoxine Ramon)

So far we've seen the development of a promising diphtheria vaccine made of toxoid (inactivated toxin, 029 and 030), but haven't seen any trials to show that this vaccine actually protects its recipients from diphtheria. Unfortunately, today's study is not such a trial either.¹

The authors were comparing the Schick test for immunity to diphtheria toxin to a test that they had developed (in the future called the Moloney test). Both involved injecting a small amount of toxin under the skin of a patient to see if they reacted to it; if so, they were not immune. The main difference was the substance used as a control: in the Schick test, heat-inactivated toxin was used as a negative control, but Moloney and Fraser here used toxoid. This approach also helped determine whether an individual would have an adverse reaction to immunization with the toxoid at full strength.

So they did this test on 141 girls, ages 10-18 years. 47% were Schick-positive, reacting to the toxin but not toxoid control; 13% were Schick-negative, reacting to neither, and thus considered to be immune; 20% reacted to the toxoid control but not the toxin; and the last 20% reacted to both. Of this last group, it's hard to tell whether they're immune or not, but could be dangerous to immunize them.

So then the authors vaccinated the 47% Schick-positive subjects with toxoid, two doses of 0.5 mL each, a month apart. They did the Moloney test again after 1 1/2 months. Of those immunized, 65% became Schick-negative, 28% didn't, and 7% reacted to both toxin and control. They tested for antibodies in the latter group and found that half of them were immune. So the vaccine converted about 70% of Schick-positive to Schick-negative; thus 70% effectiveness, according to this test.

The authors concluded that their test was reliable, though the 70% effectiveness was not great for a vaccine. Perhaps three doses would work better than two.

Papers citing this study generally acknowledged the Moloney test as a useful thing. Here are some things they say:

"The use of diluted toxoid as a control interferes with the reading of the [Schick] test by producing more marked pseudo reactions, but is therefore of great value in indicating those persons susceptible to toxic symptoms following immunizing injections of antigen."²

"The writer is of opinion that, if one test has to be omitted, that test should certainly be the Schick-control and not the Moloney injection. It has been shown that the one test cannot be used as a substitute for the other, and of the two the information given by the Moloney test is much the more important."³

Citations:
1. Moloney, P. J. & Fraser, C. J. Immunization with Diphtheria Toxoid (Anatoxine Ramon). Am J Public Health (N Y) 17, 1027–1030 (1927).
2. Loeffel, E. & Massie, E. Relative Value of Heated Toxin and Toxoid as Controls in the Schick Test. Am J Public Health Nations Health 25, 1018–1022 (1935).
3. Underwood, E. A. The Diphtheria Toxoid-Reaction (Moloney) Test: Its Applications and Significance. The Journal of Hygiene 35, 449–475 (1935).