088 - Studies in whooping cough: Diagnosis and immunization

First, the scary numbers: in 1936, there were more than 300,000 cases of whooping cough in the US, and 15% of infected infants died from it.

Leila Daughtry-Denmark wanted to help make this situation better, so this study was partially to figure out how to diagnose it early, partially to figure out how to determine who was susceptible, and partially to see if it was possible to make people less susceptible (by vaccination).

The cultures and vaccine used in this study were provided by Eli Lilly.

First Daughtry-Denmark tested white blood cell counts and agglutination to see if they correlated with infection, recovery, or immunity. Infection or vaccine seemed to increase the former but didn't seem to affect the latter.

Complement fixation (relating to antibody levels) seemed a much better indicator. Even young children (under 6 months) showed a good response to vaccination. Letting the vaccine age to 4 months didn't reduce its effectiveness. And the Georgia Public Health Lab repeated the test on their own and saw similar results. And they never observed fixation without either the vaccine or the actual disease.

Complement fixation also seemed to correlate with immunity, at least in a small sample (2 brothers), where when they were both exposed later, the brother with good fixation was protected and the other got sick.

Then there were some bigger tests of the vaccine, both with Sauer's version and a more concentrated kind that required fewer injections, making it more convenient. Apparently Sauer's sometimes took more than 8 injections to work, while this double-strength one only took three. They sure had some tolerance to shots back then; though I guess the current recommendation is four shots of DTaP before 1.5 years of age, so that's not so much better.

Anyway, there were 240 subjects who got the vaccine, but only 73 actually got exposed to the disease. Of these, 10 got the disease. So you could say it was 86% effective. But there was no control group, so it isn't possible to make firm conclusions. Also, only those who got Sauer's vaccine got exposed, so there wasn't really a test of the double-strength version.

So it seemed to work, but it's hard to know how effective it really was; exposure doesn't always mean disease, even in the unvaccinated.

A final comment mentioned in the article: there was a test of 50 college students who claimed to have had pertussis as children, and it found that only one had very good complement fixation, while 46 had no detectable fixation. So natural immunity doesn't seem that great for pertussis.

Reference:
Daughtry-Denmark, L. Studies in whooping cough: Diagnosis and immunization. Am J Dis Child 52, 587–598 (1936).