Saturday, January 25, 2014

045 - The Known and Unknown of Bacillus Pertussis Vaccine

Whooping cough, or pertussis, is caused by the bacterium Bordetella pertussis, named after a researcher named Bordet. In this study it was called Bacillus pertussis. Louis Sauer reviews many aspects of the current status (at that time) of vaccines to treat or prevent this disease.

The way the vaccines had been prepared for two decades, the organism had been grown with fresh blood in culture, then killed, preserved, and standardized to a particular number of bacteria. This was given in 3 injections, 3-4 weeks apart. But the value of this formulation was not very clear; it seemed not to prevent the disease and definitely couldn't cure it, though immunization with it might make the course of the disease more mild and less deadly, which is something.

But the disease was so serious that people couldn't give up hope in creating an effective prevention. It is most deadly in infants up to 2 years of age, and it is difficult to watch them suffer.

What they had figured out, at least, was that when studying the effectiveness, it was best to study children from 8 months to 3 years of age. Younger might be too young to work well, and in older children, the standard dose seemed to be too small (assuming they hadn't already encountered the disease).

They also knew that if 100 people were exposed to the disease, only 75 of them would catch it. So 25% should stay well. It's always hard to tell whether someone really was exposed to a disease, unless you're exposing them to it yourself, which in this case would be highly unethical. So Sauer recommends studying siblings, some vaccinated and some controls, to be extra sure of exposure. But it's still important to confirm the diagnosis in the lab.

Sauer reports that over four years, some 394 children were vaccinated with a new, differently prepared pertussis vaccine, with a much higher dose than previously. These were 14 months old, on average. The researchers observed 360 exposures of 169 of the subjects to the disease over 7 years, but the only sign of pertussis in the subjects was a mild cough in a girl that had just recovered from measles. That's good results.

So Northwestern University Medical School permitted two commercial laboratories to make this new kind of vaccines, with fresh isolates of the pathogen each month, grown in fresh human blood, and refrigerated after preparation. Sounds difficult.

But it seemed to give good results: of 127 known exposures in vaccinated subjects, only 10 resulted in pertussis; this is a protection rate of 92%. Pretty good. And most of the cases were in children over 3 who might've gotten too small a dose.

Other physicians reported around 80% efficacy (21 failures out of 130 exposures), with failures again mostly in children over 3. So it seems that the dosing for older toddlers needs modifying. It's also possible that some failures took place before the immunity had a chance to establish itself; this process seems to take three months or so after injection.

Seeing that pertussis is so dangerous for young infants, some researchers tried immunizing infants under six weeks of age. These infants were able to "withstand the injections remarkably well," whatever that means. They observed 9 exposures to the disease, and five of them got the disease. So they were probably too young to be vaccinated effectively, unfortunately.

So from this, it sounds like the newer method of preparation and dosing can be 80-100% effective, and better if given at the right age. I'd like to read the actual studies reporting these experiments before accepting these numbers though, so stay tuned.

Citation: Sauer, L. The Known and Unknown of Bacillus Pertussis Vaccine. Am J Public Health Nations Health 25, 1226–1230 (1935).

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