030 - Diphtheria Immunization with Diphtheria Toxoid (Anatoxin-Ramon)

As with the previous post (029), diphtheria toxoid—that is, detoxified toxin that can still induce an immune response—was the subject of interest for a vaccine against diphtheria. In this study, the researchers were attempting to determine the best dosing schedule and quantity for children ages 1-6.

After immunizing 572 children in total, some with two doses of 0.5 milliliters a month apart and others with 0.5 mL one month and 1 mL the next, they used something called the Schick test to determine whether the children had an adequate immune response from the vaccine. This test involved injecting a small amount of diphtheria toxin under the skin. If the person had antibodies against it, they would neutralize the toxin and show no response; otherwise, they would temporarily have a swollen red spot on their arm. So that meant, a positive test meant non-immune, a negative test meant immune. How accurate this test was, I don't know, but it's better than nothing I guess.

In terms of side effects, the authors didn't observe any problems except for 10 sore arms or general reactions; nothing severe.

Of the children that actually returned after their second dose, the authors found that about 46% of those that got two 0.5-mL doses were Schick-negative (that is, possibly immune) after 4 months. More became Schick-negative over time, so possibly up to 68% overall might be immunized by this dosing.

For those who got one 0.5-mL and one 1-mL, 71% were Schick-negative after 4 months, though many Schick-positive children had been injected from the same vial, so it might've been they just had a bad batch. Excluding those children, about 77% were Schick-negative after 4 months, and 91% after 8 months. So that's better.

Some who were Schick-positive a while after receiving their two doses were given another dose, and some up to four. Those who got three doses were Schick-negative 94% of the time, and all of those that got four doses were eventually Schick-negative (immune).

The authors admit that the sample sizes in this study were too small for definite conclusions, but from what they saw, it seemed like they could give larger quantities for better effect, that doing a Schick test to confirm immunity, and for those that lacked it, another dose should be given. It was important to have a consistent immune response, otherwise people might be overconfident in their protection from the disease, and if vaccinated people kept getting the disease, people might lose confidence in the vaccine.

Next up: Something different.

Citation: Bloomberg, M. W. & Fleming, A. G. Diphtheria Immunization with Diphtheria Toxoid (Anatoxin-Ramon). Can Med Assoc J 17, 801–803 (1927).