099 - Secondary Familial Attack Rates from Pertussis in Vaccinated and Unvaccinated Children

This study is a follow-up analysis of previous results by Kendrick and Eldering of a clinical trial in Grand Rapids, Michigan, of a whole-cell pertussis vaccine.

Rather than the whole study population, this study focused only on 165 families that were definitely exposed to pertussis from one of their own members. The other members' immunity status was known from history of vaccination or the disease itself.

What they saw was that, of all 78 vaccinated subjects, only 28 got whooping cough (36%). All these were under age 7. In contrast, of those without history of vaccination or disease, 79% got sick. Of those unvaccinated under age 7, 92% were attacked (the rate decreased with increasing age of subject). 36% vs. 92% for those most vulnerable? Not bad.

Most of the primary cases, that brought the disease to a family, were in the older category, confirming that older children often bring it to their younger siblings. Interestingly, with the subjects who had the disease before, 5 of the 6 that got sick were over 7 years old, so it seems there's a period after which the immunity is not so great, even after natural infection. The study was set up to analyze that in depth though.

Also noteworthy is that, of 172 primary cases that brought the disease to the families, 157 were unvaccinated (91%), 12 were vaccinated (7%), and 3 had the disease previously. There's some herd immunity in action, perhaps, but it's hard to tell.

This wasn't a very rigorous study (lack of blinding or placebo), but considering that an intimate exposure, such as in the same household, is probably the most difficult to have immunity against, there seems to be some effect. And apparently whooping cough is so contagious that 80-90% get sick when exposed to it this way, if not immune somehow.

References:

Kendrick, P. L. Secondary Familial Attack Rates from Pertussis in Vaccinated and Unvaccinated Children. Am. J. Epidemiol. 32-SectionA, 89–91 (1940).

O984 - Tetanus Immunization

The author of this study (Philip B. Cowles) seemed skeptical of some claims made about the tetanus toxoid vaccine, so set out to test them.¹

The first was the claim that 0.01 unit of antitoxin per milliliter of serum (the level of antibodies against the tetanus toxin in the blood) was enough to protect against the symptoms of tetanus. He used guinea pigs and mice to figure out how much antitoxin was necessary to protect. He seemed to find that 0.1 unit per mL was usually enough, though not always. As another author summarizes,

"This author felt that though 0.10 unit is not sufficiently great to protect all animals against a maximum infection, it is probably much larger than is necessary to care for many infections resulting from wounds judged to be too slight for surgical attention, and probably large enough to care for the majority of injuries that receive surgical treatment."²

The second question was how long does it take for a booster shot to raise the level of antitoxin. The common practice was to give a booster when a person presented with a wound of some sort that might expose them to tetanus infection, thinking that the vaccine would raise their antibodies enough to protect. But if that doesn't happen quickly enough, it wouldn't be very useful.

Cowles tested a number of people before and after a booster. Most had about 0.02 unit or less before, and it took 4-5 days to rise up to 0.1 or higher. Is this fast enough? Tetanus seems to develop in 7-10 days, but it's possible the toxin has started working before then, before symptoms show up. So more study would be needed to say a booster is definitely helpful, but it's pretty definitely better than nothing if an antitoxin treatment is unavailable.

As a final addendum, the author mentions the question of whether having tetanus makes one immune to further tetanus. There had been reports of people have tetanus repeatedly, so obviously there isn't always natural immunity, but Cowles describes a man who had recovered from a mild tetanus attack at some point, but didn't seem to have any antitoxin in his blood. So it seems like the tetanus toxin is toxic at lower concentrations than it is antigenic (capable of producing antibodies and immunity), so it's rare to become immune naturally without dying or something. Small sample size though.

References:

1. Cowles, P. B. Tetanus Immunization. Yale J Biol Med 9, 409–416 (1937).
2. Gold, H. Active Immunization Against Tetanus. Ann Surg 114, 1060–1068 (1941).