Data on the Prophylactic Value of Mixed Vaccines

Proof of the prophylactic value of mixed vaccines for epidemic influenza depends entirely upon the results of its practical application to human subjects in times when the disease is prevalent. Animal determinations are out of the question, because it has not been possible to produce the epidemic form of influenza experimentally. If all people were equally susceptible and were equally exposed, it would be a simple matter to compare the number of vaccinated persons who developed the disease with the number of unvaccinated persons who contracted it; but since many thousands were vaccinated and some of them contracted the disease in spite of it, and a greater number of persons who were not vaccinated entirely escaped, the analysis is extremely difficult.

The time element is a big factor. In instances where vaccination was completed in a community before the epidemic appeared there, the figures are worth more than those in which vaccination was undertaken after the epidemic had become established. This is true, because the most susceptible persons in a community developed the disease as soon as they were exposed, the less susceptible ones were not attacked until later, and the insusceptible ones escaped altogether. Whenever vaccination is begun during an epidemic, the persons vaccinated for prophylactic purposes are necessarily chosen from those who have not yet developed an attack. The later in the epidemic that vaccination is begun, the greater will be the number of persons selected for vaccination from among those more or less naturally immune. Then, if the total number of cases among the vaccinated is compared with the total number of cases among the unvaccinated, the apparent value of the vaccine is increased; but the estimation is not a fair one, because the vaccinated group is unavoidably selected from among relatively immune persons, while the controls include all of the very susceptible people who were suffering from the disease at the time vaccination was begun. Where vaccination is begun after the epidemic is advanced, the only figures worth while are those obtained by a day-by-day or a week-by-week comparison between the number of cases developing among controls and the number of cases appearing among those vaccinated, and by beginning that comparison at a time subsequent to the day on which the prophylactic inoculations were completed.

Aside from the interpretation of the results there is possibly a more serious reason for objecting to the beginning of vaccination during an epidemic. This lies in the danger of producing a temporary negative phase in the patient, which makes him somewhat more susceptible to natural infection for a few hours immediately following each administration.

McCoy (15) outlined the requirements necessary for an ideal vaccine experiment as follows: 1. The community should be as large as possible, and should number at least 10,000 persons. 2. The conditions under which they live should be as nearly equal as possible. 3. The turnover, or rather the change in population, should be as small as possible. 4. The social service should be efficient and reliable, so that it can be definitely ascertained when anyone becomes sick and what the disease is from which he is suffering. 5. Fifty per cent. should be vaccinated before the epidemic arrives, and the other 50 per cent. should be held as controls.

No examples were found which came up to the above requirements, but there were some instances in which vaccination was completed before the epidemic appeared, and some in which we were able to get a week-by-week comparison between vaccinated and unvaccinated groups. Most of the data which has been reported shows that vaccination was begun about the last of the second or the first of the third week of the epidemic, and in some instances not until after the peak was passed. Add to this the fact that the vaccine was given in from three to four doses, at from three to seven day intervals—a course which required in the neighborhood of two weeks for completion—and it is obvious that the full protective powers of the vaccine were not acquired by the individual until the worst of the epidemic was over and the number of cases were rapidly subsiding.

In order to get the best understanding from these experiments, the data will be presented in three series: I. Those instances in which vaccination was completed before the epidemic appeared. II. Those instances in which it is possible to compare the relative occurrence of influenza in both the vaccinated and unvaccinated groups after vaccination was completed. III. Those instances in which vaccination was begun after the epidemic appeared and in which comparisons of total figures only are available.

Series I. Those Instances in Which Vaccination Was Completed Before the Epidemic Appeared

1. The only instance in the Pittsburgh community in which vaccination was completed before the epidemic appeared is that reported from the Dixmont Hospital, Dixmont, Pa., and furnished me through the courtesy of Dr. Hutchinson (16). The institution had a population of about 1,000 patients and 300 employees. Prophylactic vaccination was begun on October 20, and was completed about November 6. Each c.c. of the vaccine used contained 200,000,000 each of B. Pfeiffer, Micrococcus Catarrhalis, B. Friedlander, Pneumococci, Streptococci and Staphylococci, both Aureus and Albus. Four doses were given of 4 minims, 8 minims, 12 minims and 16 minims, respectively. Inoculations were carried out at four-day intervals. Owing to the isolation of the institution from the general community, the first case did not appear until two weeks later—namely, on November 20. The results are shown by the table.

Population.No. of Cases.% of Cases.No. of Deaths.% of Deaths.
Vaccinated600447.3%00%
Unvaccinated700699.8%91.2%