Studies on Epidemic Influenza: Comprising Clinical and Laboratory Investigations

Part 12

Chapter 122,968 wordsPublic domain

(a) Their first group numbered 4,950 persons in quarantine at the Naval Training Station. The quarantine was maintained for 24 days, and no influenza appeared during that time. Three thousand five hundred and fourteen of them were released at a time when there were still 200 to 300 cases of influenza being reported daily in San Francisco. Out of the 3,514 men, 15 had influenza, and there were no deaths.

(b) At the Mare Island Navy Yards 1,950 marines were released immediately after completion of the inoculation. They were turned into Valejo and San Francisco, where influenza was at its height. Only 35 cases, with 1 death, occurred, and these developed shortly after the men were released in San Francisco. This group was controlled with an unvaccinated group of 8,232 persons who remained at Mare Island, and 1,296 cases of influenza, with 65 deaths, occurred among the controls.

(c) At San Pedro 3,100 were vaccinated, and of these 53 had influenza, and there were no deaths. The occurrence among these was compared with the prevalence of the disease in Los Angeles, but this part of the report leaves much to be desired in the way of the relative dates, etc.

(d) The fourth group, consisting of 1,080 civilians, developed 14 cases, with no deaths. However, vaccination of this group was not completed until 21 days after the pandemic had appeared in the community. Minaker’s and Irvine’s analyses show a favorable percentage for vaccination in the first two groups, but their groups three and four were not sufficiently well controlled to be of much help.

4. In a report which appeared during October, 1918, Eyer and Lowe (29) published the results of prophylactic inoculation of 1,000 New Zealand troops with a mixed catarrhal vaccine. They controlled their experiments with 19,000 New Zealand troops who were not inoculated. A comparison of the incidence of acute respiratory disease and influenza during the primary wave of the epidemic as it appeared during June and July, gave two cases among the vaccinated troops and an average of 43.2 cases per thousand among the controls.

Later they reported (58) the results of much larger experiments as carried out at 17 different camps and hospitals. The vaccine which they used was a typical “mixed” vaccine, save that the authors emphasized the advantage of using strains not more than three generations removed from the body. At some of the camps their reports were unfavorable, but upon the whole their results, as summarized below, were most encouraging. In most instances inoculations were completed just prior to the arrival of the autumn epidemic.

Out of a total average strength of 21,759, approximately 16,104 men received full prophylactic vaccination, and approximately 5,700 were uninoculated, or had received only 1 dose; 3,366 cases of influenza developed—15 per cent.; 1.3 per cent. occurred among the vaccinated, while 4.1 per cent. developed in the uninoculated; 8 per cent. of the severe cases among the protected died, as compared to 23 per cent. among the uninoculated. The death rate for all infected cases was 0.26 per cent. among the inoculated and 2.2 per cent. among the uninoculated.

NOTANDA.—All of the above reports, comprising the “Series I” experiments, indicate that mixed vaccines reduced the number of severe illnesses and lowered the death rate to some extent.

_Series II. Those Instances in Which It Is Possible to Compare the Relative Occurrence in Both Vaccinated and Unvaccinated Groups After Vaccination Was Completed_

1. The report on prophylactic vaccination at the Hospital for the Insane at Retreat, Pa., was very kindly furnished by Dr. Charles B. Maberry (20). When the epidemic approached, the institution was placed in quarantine and remained free from influenza until October 28, when two cases appeared in nurses who had broken quarantine. Influenza spread in the male ward, but the female wards were kept free during the whole of the epidemic. There were 370 male patients, but 60 were in the infirmary and were not included in the calculation. Out of 310 patients, 210 received vaccines. Ordinary commercial mixed vaccine was used, and vaccination was begun two days after influenza appeared. During the first week there were 40 cases of influenza, 6 of which occurred among those who had received a single dose of the vaccine. After the first week there were 38 cases of influenza, with 10 pneumonias and 5 deaths, among the unvaccinated, giving a morbidity rate of 38 per cent. and a mortality rate of 5 per cent. In the vaccinated group there were no cases after vaccination was completed. Maberry states further that in ward III the only cases which appeared subsequent to vaccination were in six patients who refused preventive inoculations. This appears to be the most favorable of any of the reports.

2. Nurses on duty in hospitals everywhere suffered greatly from influenza, and those of Pittsburgh were no exception. Some of the hospitals vaccinated the nurses during the epidemic and some did not, and it was hoped that by getting a week-by-week comparison of the number of cases among vaccinated and non-vaccinated nurses some reliable data would be obtained. A circular letter sent to all of the hospitals in the community contained a blank asking for the number of nurses, date of appearance of the epidemic, use of vaccine, dates of inoculations, and for a week-by-week occurrence of influenza in each group. Only 7 hospitals complied with the request, and of them only 5 sent complete data. Complete reports were received from the Allegheny General, Columbia, Presbyterian, South Side and St. Francis Hospitals. Of a total of 336 nurses in these 5 institutions, 38 developed influenza in the first week, 48 in the second, 39 in the third, 43 in the fourth, and 45 subsequent to the fourth week, making a total of 213—a morbidity of 63 per cent. The Mercy and St. Margaret’s Hospitals reported the total number of nurses and the occurrence of influenza among them, and adding in their reports there were 521 nurses on duty in 7 hospitals, with 257 cases of influenza, giving a morbidity rate of 50 per cent.; 28 cases of pneumonia and 11 deaths, giving a 2 per cent. mortality rate. The total figures from hospitals where vaccines were used are against vaccination, due partly to the fact that vaccination was started late. In these hospitals the morbidity was 66 per cent. and the death rate 3 per cent. In the hospitals where vaccines were not used the morbidity rate was 20 per cent. and the death rate 1.2 per cent. No dependable data was obtained, but the report from the South Side Hospital was interesting. Of 60 nurses on duty, 36 had influenza and 2 died. Of this number 19 were stricken the first week. Three days after the first cases were admitted to the hospital vaccination was begun, and was given to most of the nurses still on duty. Of those taking vaccines 20 developed influenza and 1 died during the period of immunization, but after the inoculations were completed there were no more cases in either group.

During the epidemic it was said that benefit was derived from the use of vaccines on nurses at the West Penn Hospital, but the writer was unable to obtain a report from this institution. The collected data on nurses was useless, though it is interesting, in that it shows the possibility of making figures prove almost anything you want them to prove.

_Series III. Those Instances in Which Vaccination Was Begun After the Epidemic Appeared, and in Which Comparisons of Total Figures Only Are Available_

Undoubtedly the largest attempt at prophylaxis against epidemic influenza through the use of “mixed vaccines” was that made under the direction of Dr. W. O. Sherman for the Carnegie Steel and H. C. Frick Coke Companies. The results which Dr. Sherman hoped to attain when he planned using the vaccine and collecting the data have already been given. Commercial mixed vaccines similar to those described under the “Series I” experiment were used, and four doses, three days apart, were given. Inoculations were begun on October 20, 1918, and were completed during the first week of November. Vaccine was administered to the employees and their families without charge. Later cards were given to all employees, and they were made to fill them out and return them. On the cards were blanks calling for the name, age, sex, color, number of inoculations, whether or not the employee himself or any member of his family had had influenza, and how many days the sick individuals had been in bed. Each mill and mine was then supplied with a set of blank forms providing for a complete statistical record of the number of inoculations and the total incidence of influenza, pneumonia and death. From the reports of the respective mills and mines the total figures given in the charts were compiled.

Difficulties were encountered in every part of the work. The vaccine demand was so great that the products of three different firms were used. So many doctors were in service that most of the vaccine had to be given by carefully coached nurses. The bulletins of the United States Bureau of Public Health and of the Allegheny County Medical Society, with their warnings about influenza vaccines being only in the experimental stage, appeared just at the time the work was begun and caused a great many to refuse to complete vaccination after one or two doses had been given. So few medical men were left that it was impossible to have them see all cases and so determine the nature of many of the illnesses which were occurring. It was assumed, therefore, that any employee who had fever and was sick for a period of three days had influenza, and that any who were confined to bed for seven days or more had pneumonia. The figures of the central offices were made up from the reports of 14 steel mills, 1 cement factory, 4 warehouses and 57 mining districts. The accuracy of data depended on the careful work of a great many local statistical workers, which made individual variations hard to control. The greatest difficulty of all, however, lay in finding a common basis for comparisons of the incidence of influenza, pneumonia and death in the vaccinated and non-vaccinated groups, since the data on the former group included the occurrence only after the peak of the epidemic had been passed, and that of the latter group included the occurrence for the entire epidemic.

The total figures are given in the three charts.

CHART I.

CARNEGIE STEEL COMPANY.

All Works Except Homestead, City Mills, Columbus, Lucy and Isabella.

STATISTICAL REPORT ON INOCULATION AGAINST INFLUENZA.

1. Number of employees who had influenza 5,728 18%

2. Number of employees who did not have influenza 24,956 —————— Total number of employees 30,684

3. Total number of persons inoculated One inoculation 2,983 Two inoculations 3,675 Three inoculations 4,626 Four inoculations 10,053 —————— Total 21,337

4. Cases influenza developed after No inoculations 2,133 23% One inoculation 745 25% Two inoculations 776 21% Three inoculations 794 17% Four inoculations 1,280 12% —————— Total 5,728

5. Cases influenza pneumonia developed after No inoculations 804 37% One inoculation 356 48% Two inoculations 403 52% Three inoculations 321 40% Four inoculations 459 36% —————— Total 2,343

6. Deaths from influenza and “flu Pneumonia” after No inoculations 104 4.7% One inoculation 32 4.3% Two inoculations 33 4.2% Three inoculations 21 2.6% Four inoculations 33 2.5% —————— Total 223 3.9%

CHART II.

H. C. FRICK COKE COMPANY.

STATISTICAL REPORT ON INOCULATION AGAINST INFLUENZA.

1. Number of employees who had influenza 5,248 31.4%

2. Number of employees who did not have influenza 11,464 —————— Total number of employees 16,712

3. Total number of persons inoculated No inoculations 3,122 One inoculation 2,483 Two inoculations 2,548 Three inoculations 3,550 Four inoculations 5,009 —————— Total 13,590

4. Cases influenza developed 47.9% after No inoculations 1,495 of (3 One inoculation 634 25.5% Two inoculations 770 30.2% Three inoculations 1,078 30.4% Four inoculations 1,271 25.0% —————— Total 5,248

5. Cases influenza pneumonia 6.3% developed after No inoculations 94 of (4 One inoculation 33 5.2% Two inoculations 42 5.4% Three inoculations 69 6.4% Four inoculations 85 6.7% —————— 6.1% Total 323 of (4 total

6. Deaths from influenza and “flu 2.0% No inoculations 30 of (4 One inoculation 13 2.0% Two inoculations 21 2.9% Three inoculations 16 1.5% Four inoculations 37 2.9% —————— 2.2% Total 117 of (4

CHART III.

BESSEMER & LAKE ERIE RAILROAD.

STATISTICAL REPORT ON INOCULATION AGAINST INFLUENZA.

1. Number of employees who had influenza 1,275 24%

2. Number of employees who did not have influenza 3,986 —————— Total number of employees 5,261

3. Total number of persons inoculated No inoculations 3,091 One inoculation 232 Two inoculations 249 Three inoculations 479 Four inoculations 1,210 —————— Total 2,170

4. Cases influenza developed after No inoculations 705 55% One inoculation 111 48% Two inoculations 91 36% Three inoculations 129 27% Four inoculations 239 19% —————— Total 1,275

5. Cases influenza pneumonia 40% developed after No inoculations 283 of (4 One inoculation 75 67% Two inoculations 59 64% Three inoculations 51 42% Four inoculations 69 28% —————— Total 537

6. Deaths from influenza and “flu 5.6% Pneumonia” after No inoculations 40 of (4 One inoculation 5 4.5% Two inoculations 0 Three inoculations 0 Four inoculations 3 4.3% —————— Total 48

Charts I and III show a decrease in the incidence of influenza in direct proportion to the number of inoculations given. This finding would have been very important had vaccination been completed before the epidemic appeared. There is, however, no convincing evidence in either of these charts that the vaccine cut down the relative number of pneumonias, or decreased the death rate to any appreciable extent. Chart I also shows the interesting fact that influenza occurred slightly more often among those who had one inoculation than among those who were not vaccinated at all.

Chart II would indicate that influenza occurred much less frequently in the vaccinated than in the control group, but a closer analysis brings out the contradictory finding that influenza occurred at the same rate in the group of 634 persons who had only 1 dose that it did in the group of 1,271 who completed the course.

The reports from the separate communities were so conflicting that to attempt to analyze them leads only to confusion.

No reports of harmful effects from the use of the vaccine were received, and several physicians who attended sick employees say that, even though the figures do not show it, they feel certain that the vaccinated persons in general were not as sick as those who were not vaccinated.

On account of the conditions under which the vaccinations were done and the reports compiled, Dr. Sherman has not felt justified in making a report, fearing that erroneous conclusions might be drawn from the data. We are greatly indebted to him for the use of his reports, without which our account of the influenza epidemic in Pittsburgh would have been very incomplete.

2. Another large steel corporation who used vaccine but asked that their names be withheld furnished the following report. During the epidemic the company offered free vaccination to its 27,000 employees and their families. Commercial mixed vaccines were used, three injections given, and vaccination begun on October 19, which was about the time of the peak of the epidemic in Pittsburgh. The results include a record of all employees who lost over six days between October 1 and November 30.

───────────────────────────────┬────────────┬───────────┬─────────── EMPLOYEES │ MORBIDITY │ PNEUMONIA │ MORTALITY ───────────────────────────────┼──────┬─────┼─────┬─────┼─────┬───── │ No. │ % │ No. │ % │ No. │ % ───────────────────────────────┼──────┼─────┼─────┼─────┼─────┼───── Received only one dose 3,895│ 511│13.13│ 31│ 0.8│ 28│ 0.72 Received only two doses 3,329│ 414│12.44│ 40│ 1.2│ 19│ 0.57 Received all three doses 9,897│ 468│ 4.75│ 46│ 0.46│ 32│ 0.32 ───────────────────────────────┼──────┼─────┼─────┼─────┼─────┼───── Total of above 17,119│ 1393│ 8.14│ 117│ 0.68│ 79│ 0.46 Received no doses 10,036│ 1522│15.17│ 154│ 1.53│ 106│ 1.06 ───────────────────────────────┼──────┼─────┼─────┼─────┼─────┼───── Total for both groups 27,155│ 2915│11.66│ 271│ 1.10│ 185│ 0.76 ───────────────────────────────┴──────┴─────┴─────┴─────┴─────┴─────

Before satisfactory conclusions can be drawn from these figures it is necessary to know how many of the 10,036 persons became sick before vaccination, and whether or not the rate of decrease in this group was not similar to that shown by the number of patients who developed influenza during the intervals between their doses of vaccine. The relatively high percentage of cases following the first and second doses are capable of explanation on one, or perhaps on all, of the three following grounds: (a) the general subsidence of the epidemic, which showed a rapid decrease by the time the third dose was given; (b) the increased protection afforded by the three doses of vaccine, and (c) the broken resistance of the patient following sudden sensitization by the vaccine.

3. Rosenow (21) prepared a mixed vaccine by growing the various bacteria in glucose broth, for from 18 hours to 36 hours, centrifuging and suspending the sediment in salt solution and making up the vaccine on a percentage basis.

FORMULA OF VACCINE

Pneumococci, Types I (10 per cent.), II (14 per cent.) and III (6 per cent.) 30 per cent. Pneumococci Group IV and the allied green-producingdiplostreptococci described 30 per cent. Hemolytic Streptococci 20 per cent. Staphylococcus Aureus 10 per cent. Influenza bacillus 10 per cent.