O1010 - Active Immunization Against Tetanus

This study looked at antibody levels in subjects immunized with various kinds of tetanus vaccine. So nothing that new. But the discussion was pretty interesting:

"The first dose of alum precipitated toxoid affects the antitoxin producing cells of the body in such a manner that following a second injection there is a rather prompt increase in the antitoxin content of the blood. A certain period of time must elapse between these two injections before this release of antitoxin into the blood stream takes place...The effect of the first dose of alum toxoid is rather unique in that it cannot be replaced by the natural occurrence of tetanus and recovery from it. We have had occasion to confirm Cowles' finding that a patient who had recovered from tetanus 10 years before still required two doses of alum toxoid before any demonstrable antitoxin appeared in the blood. Following the second dose, a few days elapse before a protective titer develops. Hence, if an injury occurs during the interval between the two injections of alum toxoid and for a week or two following the second injection, passive immunization may be necessary in order to get full protection against tetanus."

"The 'repeat' or stimulating dose of plain or alum precipitated toxoid produces within one week a remarkable increase in the antitoxin content of the blood. In most cases about five days elapse after the injection of the 'repeat' dose before the antitoxin titer is brought up or above the protective level. It is stated that the period of incubation of tetanus in man is usually from six to 14 days and is directly proportional to the amount of toxin and the severity of the disease. With a short period of incubation, six days or less, the disease is almost invariably fatal. Whether the mobilization of antitoxin that occurs after the injection of the 'repeat' dose is fast enough to prevent all cases of acute tetanus is not definitely known, but more than likely it will be able to do so, since our minimum protective value of 0.1 unit is a conservative one."

"From our studies to date, it would appear that active immunization against tetanus by means of the injection of two doses of alum precipitated toxoid followed by a 'repeat' injection upon the occurrence of an injury, will prove to be of value in military practice, in civil life where frequent injuries make the repeated injection of tetanus antitoxin impossible, and in the handling of allergic individuals who are sensitive to horse serum."

So that's interesting, and explains how things pretty much still work today, except that Td is given upon injury only if one hasn't received it for a number years.

Reference:

Gold, H. Active Immunization Against Tetanus. Ann Intern Med 13, 768–782 (1939).

101 - Prophylaxis and treatment of whooping cough with a pertussis antigen

This was an unusual study on a vaccine-like method of protecting children from whooping cough. Instead of using whole killed bacterial cells, they grew the cells and filtered them out, leaving only soluble factors the bacteria had produced externally, which they called "antigen." Then they inactivated this antigen so it wouldn't cause any problems but would still induce an immune response, treating it with formaldehyde and mild heat. This was sorta like how tetanus and diphtheria toxoid vaccines were produced.

Then they tested this antigen for how well it could a) treat whooping cough cases, b) prevent catching the disease when given when not at risk, and c) prevent catching the disease when given after being exposed.

Antigen Therapy
They had two main groups: children with whooping cough treated with antigen, and control children with whooping cough. The controls were treated with either vaccine or vaccine + antigen. They don't specify what they mean by "vaccine;" details are pretty sparse in general.

The average time before each group was similar, about 1.5 weeks, but the duration of disease after treatment was about 1.6 weeks for the antigen-treated and 3 weeks for controls, so a pretty big difference.

The number of complications in the groups was different too: About 0.7% of the antigen-treated had complications from the disease (bronchitis, conjunctival hemorrhage, otitis media), while 18% of controls had complications, including some deaths

Antigen Prophylaxis
Of those immunized without first being exposed, about 81% of those who did become exposed didn't get the disease, so they said it was 81% effective. That's not exactly how such trials should work; there should be controls.

They claimed this immunity lasted at least 5 months and up to 2.5 years, but I'm not sure how they determined this.

The same was true of those treated after being exposed: 76% didn't get the disease, but again there were no controls reported.

In terms of adverse reactions, some few patients had a short, mild fever, arm redness, or hives, but nothing worse.

Conclusions
So considering the lack of details, controls, and blinding, and how this approach didn't seem to be considered worthwhile either before or after this study, I'm not convinced it's very valuable.

Reference:

Joslin, C. L. & Christensen, T. A. Prophylaxis and treatment of whooping cough with a pertussis antigen: Report of results. Am J Dis Child 60, 1269–1276 (1940).