10. Cadham (28) reported on inoculations in a military hospital and in the civilian population near Winnipeg. Of 282 vaccinated soldiers admitted to the hospital, 17 had pneumonia and 5 died. Of 238 not vaccinated, 41 had pneumonia and 17 died. Among 24,184 civilians given two doses, 9.7 per cent. had influenza and 0.5 per cent. had pneumonia and 0.09 per cent. died. Among 85,941 controls, 24.8 per cent. had influenza, 2.2 per cent. pneumonia and 0.66 per cent. died. Cadham states that most of the inoculations were made early in the epidemic, but no accurate statistics were kept on the point.
11. A conference was held at the British War Office on October 14, 1918 (30), to discuss prophylactic vaccination and vaccines for treatment of influenza. Elaborate plans regarding dosage and gathering of statistics were made.
Notanda.—For reasons already given, the reports in Series III fail to give very reliable data on which to base a knowledge of the value of preventive vaccination against epidemic influenza.
The Attempt to Prevent Pneumonia as a Complication of Influenza Through the Use of Lipovaccine
Whitmore, Fennel and Peterson (31) developed a method of preparing an oily suspension of killed bacteria which they called “lipovaccine.” The method was used at first in making typhoid and dysentery vaccines. The advantages of lipovaccines (32) over salt suspensions are: the prevention of autolysis of the bacteria, thus increasing the length of time during which the vaccine remains active; the slow absorption of the dose, allowing the patient to continue to absorb immunity-producing substances over a period of days or weeks; the administration of a single massive dose, which does away with the three doses necessary when salt suspensions are used; and perhaps, also, the direct reduction in the toxicity of the dose by the lipoid material.
Based upon the classification of pneumococci by Dochez and Gillespie (33) in this country, and by Lister (34), (35), (36) in South Africa, and upon the latter’s successful use of anti-pneumonia vaccine on the Rand, an anti-pneumonia lipovaccine was prepared at the Army Medical School which contained approximately 10,000,000,000 each of types I, II and III pneumococci. The vaccine was made by growing the pneumococci in dextrose broth, centrifuging them out of the broth with a sharpless milk centrifuge, drying the sediment at 55° C., weighing it out so that each cubic centimeter of the finished vaccine contains 0.83 m.g. of each type, and making a suspension of them in olive oil. More recently cotton-seed oil has been used.
The result of the use of a salt suspension pneumococcus vaccine at Camp Upton was published by Cecil and Austin (37). A study of the agglutination and protective power of the serum of 42 persons vaccinated against pneumococcus types I, II and III demonstrated that a definite immune response could be secured to types I and II but not to type III. Twelve thousand five hundred and nineteen men were vaccinated at the camp, and most of the men received three or four inoculations at intervals of from five to seven days. The men were under observation for ten weeks, and during that time no cases of pneumonia of the three fixed types occurred among those who had received two or more injections. In a control of approximately 20,000 men there were 26 cases of pneumonia of types I, II and III. The incidence of pneumococcus type IV pneumonia was less among the vaccinated than among the unvaccinated groups. There were, however, 17 cases of pneumonia among the vaccinated men, compared to 173 cases of pneumonia among the controls. The annual pneumonia death rate for vaccinated groups in the army was 0.83 per one thousand, and for unvaccinated groups was 12.8.
Fennell reported the use of pneumo-lipovaccine in Washington during the influenza epidemic, but the number of cases cited by him were too small to permit of definite conclusions. His results appeared favorable.
Cecil and Vaughan (37a) reported on the results of vaccination with pneumo-lipovaccine at Camp Wheeler; 13,460 men, comprising 80 per cent. of the camp, were inoculated. Most of these men were under observation for 2 or 3 months after vaccination, and there occurred among them 32 cases of pneumococcus types I, II and III pneumonia. In one-fifth of the camp which was not vaccinated there occurred 43 cases of pneumonia. They observed that influenza caused a marked reduction in the resistance to pneumonia among vaccinated as well as non-vaccinated men. Of 155 cases of pneumonia of all types, which developed one week or more after vaccination, 133 were secondary to influenza. The death rate among vaccinated men one week or more after vaccination was 12.2 per cent., whereas the death rate for 327 cases of all types of pneumonia which occurred among unvaccinated groups was 22.3 per cent. The death rate for primary pneumonia among vaccinated groups was 11.9 per cent., and among unvaccinated 31.8 per cent. It was found that protective bodies do not begin to appear in the serum after lipovaccines are given until the eighth day after the injection. Twenty-four cases of pneumonia occurred in the first week after vaccination. In their conclusions Cecil and Vaughan state that there was no evidence whatever that pneumococcus vaccine predisposed the individual, even temporarily, toward either pneumococcus or streptococcus pneumonia. Most of the reactions after vaccination were mild, but one disagreeable feature was that in a certain percentage there persisted a small fluctuating mass at the site of the injection. Lacy saw a number of these cysts aspirated, and the contents were found to be a sterile, oily fluid, with many leucocytes present. In one instance the primary reaction disappeared within a few days after vaccination, but recurred after four months and persisted for several weeks.
Notanda.—The army lipovaccine apparently offers a certain definite amount of protection against pneumonia, which was the most dangerous complication of influenza. The protective substances do not appear in the serum until eight days have elapsed after the vaccination, and while no definite evidence has appeared to show that there is a temporary increase in susceptibility immediately after vaccination, the best results would undoubtedly be obtained where the dose is given something more than eight days before the appearance of the epidemic. The indications are that the vaccine will not protect against influenza, but that the complication of pneumonia is less likely to occur in the vaccinated than in the unvaccinated individual.