041 - The Protection Afforded by Vaccination Against Secondary Invaders During Colds in Infancy

Compared to the previous post, this story is nice and simple and straightforward, and positive.

Previous studies had tried to prevent the common cold, sometimes in combination with other respiratory infections (026 and 031). Obviously these attempts didn't work (especially since they contained only bacteria, and colds are viral infections), though they helped with pneumonia sometimes.

With this in mind, Yale Kneeland, Jr. observed that in the fall, respiratory infections were usually mild and viral (common colds), but that later in the winter, there were more and more complications and secondary infections with dangerous bacteria, causing pneumonia, fevers, etc. And if vaccines couldn't prevent the colds themselves, maybe they could reduce the severity of the illness overall?

A previous study in Norway, in which 500 infants were vaccinated against bacteria and 500 were not, showed a 5-fold reduction in fevers and a smaller number of serious complications of colds.

So Kneeland enrolled 46 infants, averaging half a year old, in the Home for Hebrew Infants in New York City, 23 as controls and 23 to receive vaccinations. The vaccines consisted of three species of pathogen: pneumococcus, hemolytic streptococcus (the kinds that caused scarlet fever, rheumatic fever, and some other things), and Haemophilus influenzae, which causes pneumonia. These bacteria were all grown up, killed (with heat and phenol), and injected whole.

There were two courses of weekly injections for the vaccinated group: the first in October, 9 injections, and the second the following February, 7 injections. Seems like way more than would be acceptable these days. Three of the subjects had fevers in February, so they missed much of the second course of injections. They were still included in the study though.

In terms of side effects, they were mild. Larger doses of vaccine caused local redness and such, but there were no fevers or anything more serious.

So now, the results: first, the two groups of subjects were no different in terms of the mild "common cold" infections they experienced. Which makes sense.

The real difference was in the number of days each group suffered a fever of more than 100°. Here is the graph from the paper:

Chart 1, Kneeland, 1934

Not much difference between groups until after the first course of vaccinations, but then the control group had many more days than the vaccinated (3 times more in January, almost 2 times more in February). Pretty striking.

The actual number of infections per subject was not much different: 5.4 in vaccinated vs. 5.8 in controls. But the severity was the big difference. The controls had 5 cases of pneumonia and the vaccinated only 2 (one of which started early in the first course of injections, probably before immunity had taken effect).

Overall, these are good results, but there are a number of problems. First, the number of subjects and infections are pretty small, so it's difficult to make good comparisons. There didn't seem to be any placebo for the controls, or any blinding, or much indication that the two groups were matched very well. Also, the number of injections is pretty high and the benefit not super great (2-3 days of high fever per infant in a given month? Seems like there's room for improvement. Also, the immunity from the first course seemed to drop after only a few months). Not quite ready for prime time, but seems like a step in the right direction.

Citation: Kneeland, Y. The Protection Afforded by Vaccination Against Secondary Invaders During Colds in Infancy. J Exp Med 60, 655–660 (1934).