Previously on the Diphtheria Vaccine Show (or whatever), we saw that toxoid (or inactivated diphtheria toxin) had good potential for immunizing safely, since an immune response against the toxin effectively prevents serious disease. People had been using mixtures of toxin with antitoxin antibodies, but this was risky, so inactivating the toxin just enough that it didn't cause disease but still induced an immune response was better. Also, something called the Moloney test, in which a small amount of toxoid was put under a patient's skin, could detect if an individual was likely to have a severe reaction to toxoid immunization. If so, they could receive a modified dose or something safer, such as a mixture of toxoid and antitoxin serum.
So the current study by H.A. Raeburn examined this question somewhat. He compared results of Schick and Moloney tests for a number of patients. Recall that the Schick test, in which a small amount of intact toxin was placed just under the skin, to see how a patient reacted, was a measure of the patient's immunity: if there was a very positive reaction, the patient was not immune (because they couldn't neutralize the toxin), and if negative, the patient was immune. The Moloney test seemed rather opposite: a positive reaction showed immunity, because the patient's immune system was overreacting to it and causing the reaction. But there was a lot of overlap between the tests, so worth doing both.
Giving a full dose of straight toxoid to a sensitive individual could cause very unpleasant reactions, including headache, vomiting, fever, and overall illness for three days, though recovery was likely I think. So the Moloney test was important, and effective, for avoiding such reactions.
However, mixing toxoid with antitoxin was not risk-free either, since the antitoxin serum often came from horses, so there were other components in it that could induce an immune response. So a person injected more than once with horse serum often developed serum sensitivity, kind of like an allergy probably. And since some diseases at that time, such as scarlet fever, could be treated best only with serum, using up a person's chance at risk-free serum treatment on diphtheria immunization wasn't always the best idea. That is to say, a person could usually count on one serum treatment being okay, the next being more risky, the third even worse, etc. So if possible, it was good to avoid using serum in combination with diphtheria toxoid, because then if the person later needed serum to treat scarlet fever or something, the risk of negative reaction was lower.
Raeburn did a small experiment to test this hypothesis, that toxoid-antitoxin led to higher toxin sensitivity. He tested the serum sensitivity of a number of subjects (using similar methods as with the Schick and Moloney tests), then immunized them either with straight toxoid or toxoid-antitoxin mix, and then tested their serum sensitivity again. Sure enough, more of those immunized with a toxoid-antitoxin mix exhibited serum sensitivity afterwards.
Finally, the best part of this study! Most of the papers I've read about diphtheria toxoid immunization have been focused on whether it could turn Schick-positive (non-immune) patients into Schick-negative (immune); that is, could it effectively induce an immune response? Which is important, but I haven't seen where people correlated this test status to actual immunity by doing epidemiology with diphtheria epidemics or anything like that. Maybe toxoid makes people Schick-negative but for some reason doesn't actually make them immune! Who knows?
But in this study, Raeburn actually does report the effects of a diphtheria outbreak in an immunized population. There were 120 subjects in some sort of house (maybe a hospital or prison or orphanage, it doesn't say), all immunized with toxoid. And there was an outbreak of tonsillitis going around, showing that it was possible and likely that all the subjects were exposed to contagious diseases that spread by droplets through the air, the way diphtheria spreads. But among these 120 vaccinated subjects, only two of them came down with the disease.
This isn't super-great data, since there's no control group, so we have no idea just from this how many we would've expected to catch diphtheria if none of them had been immunized. It seems likely that it'd be more than two, and there's probably some other data from the time period to give some idea, but I don't know where it is. So I'll be on the lookout for better studies in the future.
Citation: Raeburn, H. A. Minor Points in Diphtheria Immunisation. The Lancet 230, 621–623 (1937).
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