072 - Progress Report on Pertussis Immunization

Other than Louis Sauer and Madsen and others, Pearl Kendrick and Grace Eldering were trying to develop a good pertussis vaccine. They did a trial of the one they made in Grand Rapids, Michigan, which from what I can tell was pretty historic. This report was not their final conclusion, but they had enough data to make an interesting preliminary report.¹

They used a virulent strain of B. pertussis for the vaccine, growing it on sheep’s blood, then killing it with merthiolate (AKA thiomersal or thimerosal) or phenol. In terms of dose, they used closer to Sauer’s preferred dose, much higher than Madsen’s, but tried a few different doses (though this didn’t seem to make much difference).

The subjects in the study were children, 8 months to 5 years old, especially 1-2 years. As controls, they followed children the same age, preferring children in the same families as those who received the vaccine (to ensure similar circumstances).

They worked with nurses from the city’s public health department to follow up with the subjects at 3- or 4-month intervals, verifying reports of pertussis cases or exposures. Exposures were classified as definite (coming from someone in the home), indefinite (coming from elsewhere), or unknown (a case of whooping cough from an unknown source). Cases were rated by severity based on quantitative definitions of duration of disease, cough, whether there were complications, etc.

So what did they find? It was pretty good. By the time of publication, sixty vaccinated subjects had been exposed, but only four got sick. That’s less than 7% (or 0.5% of the total group, including non-exposed subjects, 712 subjects total).

In contrast, there were 63 cases in the control group, from 84 exposures (880 subjects total). That’s 75% infection rate (or 7% overall). So the vaccine seemed to protect more than 90%.

And even considering the four vaccinated subjects that got sick, their disease was either light or very light, while 85% of the control cases were of medium severity or higher.

The researchers warn that the numbers might be too small to make any solid conclusions, and the trial is not up to today’s standards (in terms of blinding, randomization, placebos, etc) but for what it’s worth it seems impressive.

A later historical account gives the following description of the response to this report. Keep in mind that requirements for trials in the 1930s were much less rigorous than they are now, and that yet Frost basically admits he can’t find much fault with the design: 

"Although it was well controlled, the 1934-1936 field trial had to surmount considerable initial skepticism within the national public health community. Shortly after Kendrick and Eldering announced their results, James Doull, a prominent Cleveland epidemiologist, reported that children received no protection from a vaccine he had designed and produced (065). The APHA subcommittee on whooping cough, which included both Kendrick and Doull, evaluated the contradictory results of the two studies but was unable to explain why they differed. The committee then asked Wade Hampton Frost, a Johns Hopkins epidemiologist and head of the APHA, to review both studies.
     Frost was predisposed to find fault with Kendrick's study. In a "personal" note...Frost voiced his doubts: 'I very strongly suspect that Miss Kendricks field studies are not set up in such a way as to give a really good control. My reason for this suspicion is that, as you know well enough, the satisfactory set-up of such an experiment is an exceedingly difficult matter. Not 1 out of 10—perhaps not 1 out of 50—attempts is successful and as a mere matter of probability the odds are strongly against Miss Kendrick's experiments being sound.'
     Unable to find the faults he expected in Kendrick and Eldering's study, Frost journeyed twice to Grand Rapids to examine their data and recommend suggestions for improving statistical accuracy and coding. In the end, Frost said to Kendrick, 'I think it may be assumed, not as a conclusion but merely as a working hypothesis, that your data when finally analyzed are likely to show some protection in the vaccinated group.'"²

Citations:

1.  Kendrick, P. & Eldering, G. Progress Report on Pertussis Immunization. Am J Public Health Nations Health 26, 8–12 (1936).

2.  Shapiro-Shapin, C. G. ‘A Whole Community Working Together’: Pearl Kendrick, Grace Eldering, and the Grand Rapids Pertussis Trials, 1932-1939. Michigan Historical Review 33, 59–85 (2007).