Chapter VII: Part 7

From the beginning to the end of an epidemic the health authorities, aided by the medical profession, should take the public wholly into their confidence. At the first news of the approach of the disease a general bulletin should be issued giving all of the main facts that are available. This was done in a way by the American Public Health Service, but the bulletin reached only a small fraction of the people, and although parts of it appeared later in the daily papers, it was pretty generally missed. The papers should be used freely and the space paid for when necessary, so that the news of the epidemic is featured emphatically. The establishment of a question and answer department or a bureau of information would take care of a great deal in the way of denying misinformation. The public should be encouraged to report helpful facts of all kinds, but with the understanding that no rumors would be published without investigation and confirmation. In this way it would be possible to prevent articles advising harmful and useless remedies from reaching the press, and aid in suppressing some of the “Sure Cures,” so many of which appeared to abuse the confidence of the unwary during the 1918 epidemic. Several such cures have been most interestingly discussed in a recent bulletin of the United States Public Health Service. The bulletin divides the “Sure Cures” into three different classes, as follows: “First comes the individual who has a specific remedy, the formula of which he will sell for a price * * *; next comes the person with a pseudo-scientific treatment, e. g., isotonic sea water, ‘orzono therapy,’ ‘harmonic vibrations.’ * * * Still another type, who gives freely of his advice that humanity may be spared from pestilence.” Among the latter are found advice for placing sulphur in the shoes, wearing of amulets, inhaling of alcohol, chloroform, etc., as well as numerous religious and mental science treatments, etc. A frank statement of facts and a discussion of the ridiculous side of many of these claims would undoubtedly benefit the entire public. The placarding of the cars and the warnings posted in conspicuous places no doubt helped greatly, and this method undoubtedly should be continued. As long as theatres are allowed to remain open, speakers may be used to advantage to emphasize important points. The County Medical Societies should be asked to appoint committees for supplying information or for seeing that the information given to the public is authoritative. In large cities committees may be organized among hospital superintendents, so that the heartiest co-operation between health authorities and hospitals will be available. The ever-ready aid of the Red Cross and of every other auxiliary body should be employed to the fullest extent to allay apprehension and relieve suffering.

_Summary_

The exact knowledge of the mode of transmission of epidemic influenza is still wanting, but it is known to be spread by contact. Attention should be directed toward every practical means of decreasing the number and intimacy of contacts. Publicity campaigns and other educational measures should be pushed strongly. Health Departments should adopt a policy of preparedness during inter-epidemic times, should make every effort to centralize and standardize their work, and should take steps to obtain sufficient legal backing, so that upon the appearance of the epidemic they can take the lead, speak with authority and enforce their ordinances and measures. The physician’s duty is to inform himself on the value of the various measures, and if he is at odds with the public health methods, he should settle them between epidemics, so that when he is called upon to carry out public health orders he can do it to the letter and without criticism. Laymen should learn that quiet living without violent exercise, the keeping of good hours, the avoidance of public gatherings and of unnecessary exposure is the best policy to pursue during influenza epidemics. They should strictly obey the orders of those who have specialized in the control of epidemics, and all business men must stand ready to help in every possible way and to make their business interests subservient to the public good.

BIBLIOGRAPHY

1. Rosenau, Keegan, Public Health Report, 1919; xxxiv, No. 2,
Goldberger and Lake p. 33.
1a. McCoy and Richey Public Health Report, 1919; xxxiv, No. 2,
p. 34.
2. Lacy Jour. Lab. and Clin. Med., 1918; iv, p. 55.
3. Wollstein Jour. Exper. Med., 1911; xiv, p. 73.
4. Flexner Jour. Amer. Med. Assoc., 1913; lxi, p.
1872.
5. Park and Williams Bacteriology, 1914 Edition; p. 437.
6. Leary Jour. Amer. Med. Assoc., 1918; lxxi, p.
2098.
7. Leary Amer. Jour. Public Health, 1918; viii, p.
755.
8. Rosenau Preliminary report furnished through
Surgeon-General of the Navy W. C.
Braisted.
9. Barnes Jour. Amer. Med. Assoc., 1918; lxxi, p.
1849.
10. Hinton and Kane The Commonwealth Mass. State Dept. Health,
1918; vi, Nos. 1 and 2, p. 28.
11. Hinton and Kane Hinton’s Report.
12. Parker Jour. Amer. Med. Assoc., 1919; lxxii, p.
476.
13. Pearce Jour. Amer. Med. Assoc., 1913; lxi, p.
2115.
14. Committee on New and
Non-Official Jour. Amer. Med. Assoc., 1918; lxx, p.
Remedies 1967.
15. McCoy Personal Communication.
16. Hutchinson Dixmont Hospital Report.
17. McCoy, Murray and Jour. Amer. Med. Assoc., 1918; lxxi, p.
Teeter 1997.
18. Minaker and Irvine Jour. Amer. Med. Assoc., 1919; lxxii, p.
847.
19. Sherman Report.
20. Maberry Report from Hospital for Insane, Retreat,
Pa.
21. Rosenow Jour. Amer. Med. Assoc., 1919; lxxii, p.
31.
22. Beaver, Boles and Case Jour. Amer. Med. Assoc., 1919; lxxii, p.
265.
23. Ely, Lloyd, Hitchcock
and Nickson Jour. Amer. Med. Assoc., 1919; lxxii, p. 24
24. Kitano Jour. Amer. Med. Assoc., 1919; lxxii, p.
1575.
25. Wynn Pract. London, 1919; cii, p. 77.
26. Norman White Lancet., 1919; i, p. 707.
27. Whitingham and Sims Lancet., 1918; ii, p. 865.
28. Cadham Lancet., 1919; ii, p. 885.
29. Eyre and Lowe Lancet., 1918; ii, p. 485.
30. Conference British War
Office
31. Whitmore, Fennel and Jour. Amer. Med. Assoc., 1918; lxx, p. 427;
Peterson also p. 902.
32. Fennel Jour. Amer. Med. Assoc., 1918; lxxi, p.
2115.
33. Dochez and Gillespie Jour. Amer. Med. Assoc., 1913; lxi, p. 727.
34. Lister Publications of the South African Institute
for Medical Research, No. 2, 1913.
35. Lister Publications of the South African Institute
for Medical Research, No. 8, 1916.
36. Lister Publications of the South African Institute
for Medical Research, No. 10, 1917.
37. Cecil and Austin Jour. Exper. Med., 1918; xxviii, p. 19.
37a. Cecil and Vaughan Jour. Exper. Med., 1919; xxix, p. 457.
38. Bloomfield Johns Hopkins Bull., 1919; xxx, p. 1.
39. Capps War Med., Vol. ii, p. 371.
39a. Capps Jour. Amer. Med. Assoc., 1918; lxx, p. 910.
40. Weaver Jour. Amer. Med. Assoc., 1918; lxx, p. 76.
41. Weaver Jour. Amer. Med. Assoc., 1918; lxxi, p.
1405.
42. Weaver Jour. Infect. Dis., 1919; xxiv, p. 218.
43. Doust and Lyon Jour. Amer. Med. Assoc., 1918; lxxi, p.
1216.
44. Haller and Colwell Jour. Amer. Med. Assoc., 1918; lxxi, p.
1213.
45. Leete Lancet., 1919; i, p. 392.
46. Dannenberg Jour. Amer. Med. Assoc., 1918; lxx, p. 99.
47. Mink Jour. Amer. Med. Assoc. 1918; lxxi, p.
2175.
48. Vaughan Jour. Amer. Med. Assoc., 1918; lxxi, p.
2100.
49. Copeland Jour. Amer. Med. Assoc., 1918; lxxi, p.
2173.
50. Lynch and Cummings Jour. Amer. Med. Assoc., 1918; lxxi, p.
2174.
51. Amer. Med. Association Public Health Report, 1919; xxxiv, p. 1413.
52. Le Moignie and Pinoy Compt. rendu. Soc. Biol., 1916; lxxix, pp.
201 and 352.
52a. Wright and Douglas Proc. Royal Soc. Med., 1904; lxxiii, p.
128, and lxxiv, p. 147.
53. Neufeld and Rimpau Zeitschr. f. Hyg., 1905; li, p. 283.
54. Rosenau Prevent. Med. and Hyg., 1918.
55. Brown, Palfrey and Jour. Amer. Med. Assoc., 1919; lxxii, p.
Hart 463.
56. Gay Typhoid fever. (Published by Macmillan Co.,
1918.)
57. Eyre and Low Lancet. I, April 5, 1919; p. 557.

PHYSIOLOGICAL AND PHYSIOLOGICAL CHEMICAL OBSERVATIONS IN EPIDEMIC
INFLUENZA

By C. C. GUTHRIE, PH. D., M. D.

The material consisted of cases in the acute stage of epidemic influenza with and without clinical pulmonary involvement (alveolar); of convalescents, and of normal individuals without influenzal history.

It was hoped that it would be possible to follow selected cases over considerable time periods, observation to compromise coordinated clinical as well as laboratory data, but the exigencies of the situation rendered this impossible. Unfortunately, this limits the value of the studies. But since similar observations were made on cases ranging from normal to the gravest severity—in fact, preceding death but a few hours in some instances—and from the nature of the findings, certain conclusions are clearly warranted.

It is regrettable that the data on certain points is not more extensive, and particularly that other methods of observation were not employed. As an example of the latter, measurements and analyses of expired air may be given, as this was planned from the beginning and unsuccessful efforts made to provide the required apparatus. In view, however, of the circumstances of the investigation, it is felt that the studies made are, on the whole, reasonably comprehensive and complete. And it is only fair here to acknowledge that this was rendered possible by the cordial and practical support of the Medical School, the military authorities, the director of the laboratories, clinical colleagues, particularly Dr. W. W. G. Maclachlan, and last, but not of less importance, of the members of the department who made the studies.

In presenting the results, it is deemed most expedient and practical to omit extensive tabulations and to summarize the data under each subject.

From the report it will be obvious that certain studies were in preliminary stages at the termination of the investigation. This was due in certain instances to the lateness of their undertaking, or time consumed in providing essential equipment and methods; or to disappearance of suitable cases due to waning of the epidemic.

RESULTS

_Circulation_

For the most part, cases showing marked clinical symptoms were studied. The pulse in severe cases frequently was weak and rapid but regular. In some cases it was less rapid than the clinical state would seem to indicate.

_Arterial Blood Pressure_ was low; systolic pressure in severe cases ranging downward from 95, and diastolic down to 40 or under. In patients in early stages of convalescence the pressure showed a marked advance toward normal levels. Arterial blood pressure seemed a reliable general index of the condition of the patient.

_Venous Blood Pressure._—The observations included patients who a few hours later expired. The Von Recklinghausen method was used. No marked abnormality was observed, so other methods of observation were deemed superfluous.

_Respiration_

In severe cases, frequently it was rapid and of shallow character; but, like the pulse, often it was less rapid than the clinical state would seem to indicate.

_Cyanosis_ of dark hue and marked degree was prevalent in the earlier severe cases, and in some cases appeared entirely out of proportion to the state of circulation and respiration and to the post-mortem findings as reported by Dr. Klotz.

_Blood_

Hemorrhage being not uncommon, the blood was tested for coagulability, but in this respect no marked departure from the normal range was noted.

_Coagulation._—Coagulation time was observed by stirring blood in a test tube with a wire and noting the time of the appearance of fibrin and by means of a Biffi-Brooks coagulimeter. The extreme ranges observed were from 2½ to 5½ minutes. The average by defibrination was 3 minutes and 36 seconds, and by the Biffi-Brooks method 4 minutes and 38 seconds.

_Red Corpuscles._—Osmotic resistance. A number of bloods were examined by observing their resistance to osmotic laking by exposure to a series of hypotonic sodium chloride solutions. Though some differences were observed, from the evidence obtained, it is not permissible to conclude that such variations were constant or of a significant magnitude.

_Color_ on exposure to air. It was early observed that venous blood from cyanotic patients was very slow to take on arterial hue on exposure to air.

_Plasma Bicarbonate._—The plasma bicarbonate was determined in seven cases by Miss Waddell by the method of Van Slyke and Cullen. In all except one of these the results were within the normal range as given by Van Slyke. Three were in the lower normal range, being 54.1, 55.1 and 60.5 respectively, expressed in terms of cubic centimeters of CO_{2} reduced to 0°, 760 mm. Hg. pressure, bound as bicarbonate by 100 c.cm. of plasma. Three were in the median range, being 64, 65.5 and 71 c.cm. In one case the bicarbonate CO_{2} was reduced to 46.6 c.cm.

There seemed to be no constant relation between the apparent severity of the clinical condition of the patient and the bicarbonate reading. In the one case in which this was found to be reduced below Van Slyke’s lower normal limit the blood was taken only a few hours before death.

_Hemoglobin Per Cent._—As determined by the Sahli hemoglobinometer (by Miss Lee) and as estimated by the total oxygen capacity (Van Slyke method) (by Dr. Rohde and Mrs. Macklin), the hemoglobin content ranged within normal levels.

_Relative Volume of Corpuscles._—A limited number of hematokrit tests on severe cases gave results in normal levels.

_Spectroscopic Studies._—Sera obtained from 20 post-mortem bloods were examined spectroscopically. In eight an absorption band in the red was observed. In some instances such a band was observed in blood obtained shortly after death and before coagulation had occurred, while other similar bloods, as well as bloods obtained at longer intervals after death, exhibited no such band. A similar band was observed in one case from blood obtained from a patient about 12 hours before death from pneumonia following influenza. Medication was not a causative factor. To ammonium sulphide the band in the red reacted as methemoglobin and the position (as estimated by Dr. Menten) corresponded with methemoglobin. Oxyhemoglobin bands in such bloods occupied normal positions as determined by Dr. Menten. On diluting such bloods with water no abnormality in character or position bands was observed, save in one instance (No. 778 below). This does not, however, disprove the possibility of such abnormality in the hemoglobin within the cells, for moderate dilution only of serum rendered the band in the red invisible, presumably by dilution.

Detailed examination of the absorption bands was made with a direct
reading wave-length Hilger Spectroscope (which was calibrated by
line spectra derived from salts added to an alcohol flame) by Dr.
Menten. This spectroscope had an accuracy of about two Angstroms. In
all, seven post-mortem bloods were examined, viz. autopsy numbers
756, 761, 763, 773, 778, 784, and 787. In five of these, sufficient
serum was obtained to make readings. All gave the two characteristic
oxyhemoglobin bands in the blue-green with centers of the bands at λ
758μμ λ and 542μμ. The second oxyhemoglobin band varied slightly in
width in the different samples. In addition to the two oxyhemoglobin
bands in each of four of the above sera, viz: Nos. 756, 763, 767 and
787, an absorption band in the red was found with the center of the
band as follows: Number 756 at λ 627μμ, number 761 at λ 634μμ,
number 763 at λ 625μμ, and number 787 at λ 634μμ. These bands varied
considerably in intensity and could only be identified when the two
oxyhemoglobin bands were merged and appeared as one broad band. As
controls for the position of the oxyhemoglobin bands two normal
bands were examined, which showed two bands with centers also at λ
758μμ and λ 543μμ. For comparison of the methemoglobin bands of the
above post-mortem bloods, a sample of this hemoglobin compound was
made by adding potassium ferricyanide to normal blood until the
solution became brownish in color. The center of this methemoglobin
band was found at λ 634μμ. In blood from autopsies number 773 and
number 778 sufficient serum could not be obtained to make a reading.
To each of these bloods distilled water was added. The laked blood
of 778 gave a methemoglobin band with the center at λ 632μμ on
examination 24 hours after autopsy. Similar treatment of corpuscles
five days subsequently gave no indication of the presence of any
methemoglobin spectroscopically.

From the serum and from the laked corpuscles of number 784 no trace
of methemoglobin was found when the blood was examined a few hours
after removal at autopsy.

_Oxygen Capacity._—The total oxygen capacity was determined by the Van Slyke method (by Dr. Rohde and Mrs. Macklin). At this stage the more pronounced type of influenza had subsided, but in early convalescence the capacity was within normal ranges.

Other studies using different technique gave concordant results, but there were indications that oxygen was more slowly absorbed than normally.

_Oxygen Content of Venous Blood_ measured by the Van Slyke method (by Dr. Rohde and Mrs. Macklin) on the same bloods examined for total oxygen capacity seemed to indicate a mild deficiency as compared to normal bloods.

_Gases, Kinds, Quantity and Rate Yielded to Vacuum._—In general it may be said that quantitative differences observed are not considered fundamental, but that the studies indicate abnormal slowness in oxygen absorption.

_Gases, Quantity and Rate of Absorption on Exposure to Air After Extraction by Pump._—The results emphasize slowness of oxygen absorption as compared to normal blood.

The material to be examined was exhausted for three minutes in the
receiver of the Van Slyke apparatus. One c.cm. was then transferred,
with as little exposure to air as possible, to a small empty bottle,
which was then closed and placed in communication with a calibrated,
horizontal tube, containing a segment of alcohol, which served the
dual purpose of a seal and an air volume change indicator. (See Fig.
1.) The apparatus was made in duplicate and mounted on a common
base, so that simultaneous readings on different samples could be
made. After establishing the zero position of the alcohol segment,
the base on which the bottles were mounted was vigorously shaken in
a uniform manner. Ten seconds after the period of shaking, the
volume readings were taken. Successive periods of shaking and
reading were conducted at 30-second intervals, until the test was
completed. Actual volume changes were then calculated, tabulated and
plotted.

The greater confidence is placed on the results obtained by
observing the color of the blood, as described below; but since then
the method has been checked up and the results indicate that the
findings were of sufficient accuracy to warrant their inclusion in
this report.[1]

Footnote 1:

Studies along this line are being made with improved apparatus, the
results of which, together with the description of the apparatus, will
be published elsewhere. (See Am. Gr. Physiol., 1920, li, 195.)

_Effect of Addition of Serum on Behavior on Exposure to Air._—The persistence of venous hue of blood exposed to air was noted above. It was observed that the addition of serum from the same blood conspicuously shortened the time required for such blood to acquire an arterial hue. The addition of normal serum was more effective in this respect than pathological serum. Measurements of the rate of absorption of such blood after the addition of serum indicated acceleration of oxygen absorption. From this it would seem that the oxygen transmitting capacity of the serum was diminished.

_Effect of Addition of Dry Sodium Bicarbonate on Behavior on Exposure to Air._—The addition of a small quantity of dry sodium bicarbonate to a blood refractory to arterialization on exposure to air enormously accelerated the process, as judged by the color. To what extent the change in color may have been due to causes other than oxygen absorption was not determined.

_Comment_

The most significant positive findings were evidence of deficiency of serum oxygen transmitting capacity or rate, and the detection in serum of an absorption band in the red corresponding to methemoglobin. The presence of the abnormal substance giving rise to the absorption band is considered of special interest as indicating abnormal chemical conditions in the blood, rather than material change in hemoglobin oxygen capacity.

THE BACTERIOLOGY OF EPIDEMIC INFLUENZA WITH A DISCUSSION OF B. INFLUENZÆ
AS THE CAUSE OF THIS AND OTHER INFECTIVE PROCESSES

By W. L. HOLMAN, B. A., M. D.

_Introduction_

In a study of the bacteriology of a respiratory disease such as influenza, the technical difficulties encountered are very great and must be overcome before we can draw useful conclusions from the results obtained or attempt to determine the etiological factors. The important methods of attacking such a problem include: (1) the study of stained smears and cultures from the various available materials, along with the demonstration of the bacteria in the lesions found in the disease by a study of sections; (2) tests with the various materials to determine the presence of the causative agent, which includes experiments on man and animals and is more inclusive than the mere study of the bacteria isolated; (3) immunological studies of man suffering from the disease, or of man and animals treated with the materials from the disease; (4) pathological, clinical and epidemiological studies linked with the above.

Many of the difficulties and sources of error in these methods are manifest to all, but certain points may be indicated as more important in the phases of the work on which I am to report.

_General Methods of Investigation_

Stained smears from the material available. The choice of the material is of first importance. Sputum to be of any real value must be obtained from the deeper portions of the respiratory tract, should be as free as possible from the secretions of the buccal cavity, and should be washed in saline before it is used. These are considered among the first requirements in the study of lung infections by the pneumococci and are equally important in influenza. Swabs from the nasopharynx should be obtained with the same precautions as are demanded in meningococcal work. The other available material—such as blood, lung puncture fluid, pleural fluid and spinal fluid—must be collected with the greatest care.

The staining methods should, naturally, include those which will bring out the various types of bacteria, and must include the Gram method, using dilute alcoholic fuchsin (1-20) as the counterstain. The varying morphology of the B. influenzæ and its frequent minute size make it difficult to detect. It is not the only Gram negative small bacillus seen in smears from the throat, but when it occurs in the typical schools, or where there are numerous bacilli to be seen, its characteristics are quite definite. I have recently isolated an anærobic Gram negative bacillus from a series of swabs from the buccal cavity which suggests in many ways the morphology of the B. influenzæ, which will indicate one of the many difficulties to be met with in the study of stained smears. They are, nevertheless, of great use as a control on cultures, and most helpful in the study of the material from sources other than the respiratory tract.

Cultures of the bacteria from the various materials. Here we have the greatest difficulty of all. The medium chosen determines the bacteria which will appear to predominate, and there is no single medium that will answer all purposes. Streptococci will appear to be in excess when serum broth is used, as I have previously shown; pneumococci with Avery’s pneumococcus medium; and staphylococci, the Gram negative cocci, and the diphtheria group with Loeffler’s serum. Ordinary blood agar is perhaps the best general medium for direct and secondary plating. There have been many special media devised for growing the B. influenzæ, but the one I have used most and found particularly helpful is heated blood agar made after the general method of Voges.

The extremely tiny colony of B. influenzæ on ordinary blood agar makes it particularly difficult to detect, and one is apt to get the wrong impression of its numbers from the macroscopic appearance of the plate. In attempts at isolation there must be a liberal use of media in picking colonies, as many suspicious ones will turn out to be immature growths of B. xerosis, M. pharyngis (or M. catarrhalis), streptococci, or more rarely pneumococci and other organisms. Replating from such picks is frequently necessary, and further plates, from the original culture on heated blood agar, must often be made before the B. influenzæ can be isolated. The care required in all stages of the isolation of this organism, the unstinted use of media for plating and for picks, the number of stained smears to be studied, and the further transfers necessary to verify results, all these limit the amount of material which can be studied with any degree of accuracy. If further the streptococci, the pneumococci, the Gram negative cocci, the capsulated Gram negative bacilli and many others are to receive any attention, it can readily be appreciated that a few cases carefully studied are of far more value than a large number hurriedly examined in an uncertain routine.

The pathological study of the same cases on which I have done the bacteriology will be found in Dr. Klotz’s paper in these communications, and I will merely refer to some of the bacterial findings in the sections of the lungs and bronchi. The more inclusive methods which have been used in attempts to determine the etiological factor in influenza we have been unable to attempt, but I will refer later in this paper to the findings of the investigations of others. Immunological studies have been limited to a few investigations on the presence of agglutinins, complement binding substance, skin reactions and the amount of complement present in the sera of certain patients. The epidemiological and clinical studies are reported by Drs. Johnston and Lichty in this series of reports.

_Material Studied_

The material used in the study I am reporting included swabs from the large bronchi and fluid from the lungs and pleural cavities of 32 autopsies, as well as blood cultures from 22 patients and swabs from the nasopharynx of 31 individuals. Fifteen sera were tested for fixation of complement with an antigen made from several strains of B. influenzæ. Fourteen other sera were tested for agglutinins. Complement content was determined in the sera of 25 patients. Skin tests after the Von Pirquet method were done on 14 convalescents, and carefully stained nasopharyngeal smears without cultures were studied from 48 patients.

The chief attention was given to the study of the autopsy material and we concentrated on the isolation of B. influenzæ. At the same time we did not neglect the other bacteria making up the flora of the bronchi, lungs and pleural cavity in these cases. The various types were isolated and most of them fully identified.

_Technique_

Direct smears were made on sterile slides of all material studied and stained by Gram’s method. The counterstain was always alcoholic fuchsin diluted 1-20 in distilled water. Direct cultures were made on a human blood agar plate containing 5 per cent. blood, which was further smeared just before use with defibrinated blood. This latter procedure was later discarded, as it did not appear to assist to any marked extent the growth of B. influenzæ. Blood broth containing a few drops of defibrinated blood and blood agar slants smeared with blood were also used. Heated blood agar (2-3 c.cm. of defibrinated human blood added to 100 c.cm. of ordinary agar at a temperature of from 90 to 100° C., or as the agar comes from the sterilizer) was used in the last nine cases to replace the blood agar slant in the direct cultures and as the medium of choice for transfers of the B. influenzæ.

I prefer the ordinary blood agar plate to the heated blood plate because the former gives readings which are very helpful in distinguishing colonies of various types. B. influenzæ appears as clear, tiny, pinpoint, inert colonies. B. xerosis or the pseudodiphtheria group gives more opaque but often rather similar colonies. Gram negative cocci as M. pharyngis siccus have dry, raised, soon becoming wrinkled, inert colonies, varying greatly in size; M. catarrhalis, more moist, inert colonies. The cocci of the streptococcus viridans group appear as very small colonies with greening, or are not infrequently inert, while thin, flattened colonies with central thickening may sometimes be noted. Those of the streptococcus hemolyticus group occur as small, frequently nipple-like colonies with clear, wide zones of hemolysis; pneumococci as moderately small, moist, dewdrop-like colonies with center collapsing early and with greening; streptococcus or pneumococcus mucosus as larger, watery, sticky colonies with greening and frequently an early clearing near the colonies.

TABLE I.

BACTERIOLOGY OF THIRTY-TWO AUTOPSIES FROM INFLUENZA CASES.

───────┬─────┬───────────┬─────┬──────────────────┬─────────────────────
AUTOPSY│DATE.│ DAY OF │HOURS│ DIRECT │ B. INFLUENZÆ
NUMBER.│ │ DISEASE. │P.M. │ SMEAR—GRAM’S │
│ │ │ │ METHOD. │
───────┼─────┼───────────┼─────┼──────────────────┼───────┬─────┬───────
│ │ │ │ │BRONCH.│LUNG.│PLEURAL
│ │ │ │ │ │ │FLUID.
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
741│ 1918│ 3│ 16│G +staph. Few │ 0 │ + │ 0
│ Oct.│ │ │ pneumo-like. Few│ │ │
│ 9│ │ │ chains of elong.│ │ │
│ │ │ │ cocci. │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
743│ 11│ 5│ 8│Br. G—bac. from │ + │ 0 │ –
│ │ │ │ coccoid to short│ │ │
│ │ │ │ threads. Mostly │ │ │
│ │ │ │ scattered. Some │ │ │
│ │ │ │ phagocyted. │ │ │
│ │ │ │ Fewer G +cooci │ │ │
│ │ │ │ in short chains.│ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
744│ 11│ 7│ 11│Br. G—bac. │ + │ – │ 0
│ │ │ │ moderately stout│ │ │
│ │ │ │ about in small │ │ │
│ │ │ │ groups and │ │ │
│ │ │ │ scattered. │ │ │
│ │ │ │ G+diploc │ │ │
│ │ │ │ (pneumo) also G—│ │ │
│ │ │ │ threads. Phago. │ │ │
│ │ │ │ of both in a few│ │ │
│ │ │ │ cells. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
745│ 12│ 10│ 6│Br. G +—large │ + │ 0 │ ––
│ │ │ │ bac., strept. │ │ │
│ │ │ │ short, G—B, few,│ │ │
│ │ │ │ very short, no │ │ │
│ │ │ │ threads. │ │ │
│ │ │ │ │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
746│ 12│ 5│ ½│Br. G—B very │ + │ – │ 0
│ │ │ │ short, no │ │ │
│ │ │ │ threads. │ │ │
│ │ │ │ Irregularly │ │ │
│ │ │ │ scattered. More │ │ │
│ │ │ │ seen in left │ │ │
│ │ │ │ bronchus. A few │ │ │
│ │ │ │ cells │ │ │
│ │ │ │ phagocyted. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
747│ 13│ 6│ 3│Br. G+diploc, │ + │ – │ –
│ │ │ │ fairly numerous.│ │ │
│ │ │ │ G—B tiny, as │ │ │
│ │ │ │ diplos and in │ │ │
│ │ │ │ long threads │ │ │
│ │ │ │ scattered or in │ │ │
│ │ │ │ small groups. │ │ │
│ │ │ │ Pleural fluid │ │ │
│ │ │ │ and lung no │ │ │
│ │ │ │ bacteria seen. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
748│ 13│ 4│ 4│Br. nothing like │ – │ + │ 0
│ │ │ │ B. I. seen. G+ │ │ │
│ │ │ │ small elong. │ │ │
│ │ │ │ diplo. Numerous │ │ │
│ │ │ │ G + diploc. in │ │ │
│ │ │ │ lung. │ │ │
│ │ │ │ Comparatively │ │ │
│ │ │ │ few Q-B, very │ │ │
│ │ │ │ short. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
749│ 14│ 4│ 15│Br. G+large pneumo│ – │ – │ 0
│ │ │ │ like, many │ │ │
│ │ │ │ G+large bacilli,│ │ │
│ │ │ │ single and in │ │ │
│ │ │ │ pairs. Few G—B │ │ │
│ │ │ │ very tiny and │ │ │
│ │ │ │ widely │ │ │
│ │ │ │ scattered; lung,│ │ │
│ │ │ │ heavy mixture as│ │ │
│ │ │ │ in bronchi. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
750│ 14│ 9│ 6│Br. G+B large like│ – │ – │ 0
│ │ │ │ B. welchii, │ │ │
│ │ │ │ G—rather stout │ │ │
│ │ │ │ coccoid forms, │ │ │
│ │ │ │ G+C in pairs and│ │ │
│ │ │ │ short chains. │ │ │
│ │ │ │ Tiny G—coccoid │ │ │
│ │ │ │ forms like B. I.│ │ │
│ │ │ │ Lung G+ │ │ │
│ │ │ │ pneumo-like and │ │ │
│ │ │ │ caps, chains; no│ │ │
│ │ │ │ B. I. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
751│ 14│ 7│ 6│Br. G +cocci large│ – │ – │ +
│ │ │ │ elong.? caps, │ │ │
│ │ │ │ also G +C in │ │ │
│ │ │ │ flat pairs. │ │ │
│ │ │ │ G—coccoid forms.│ │ │
│ │ │ │ Lung, numerous │ │ │
│ │ │ │ bacteria. │ │ │
│ │ │ │ G+strept. with │ │ │
│ │ │ │ flattened cocci.│ │ │
│ │ │ │ Some G-short │ │ │
│ │ │ │ forms? │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
752│ 15│ 13│ 15│Br. G+pneumo-like.│ – │ + │ 0
│ │ │ │ G+B smaller than│ │ │
│ │ │ │ B. welchii, │ │ │
│ │ │ │ occasionally │ │ │
│ │ │ │ tiny G │ │ │
│ │ │ │ -diplobacillus. │ │ │
│ │ │ │ Lung, G+chains │ │ │
│ │ │ │ of cocci Gram │ │ │
│ │ │ │ weak. Few G—tiny│ │ │
│ │ │ │ bacilli │ │ │
│ │ │ │ scattered or in │ │ │
│ │ │ │ groups. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
756│ 16│ 8│ 18│Br. numerous G+B. │ – │ 0 │ –
│ │ │ │ B welchii like. │ │ │
│ │ │ │ G—B large and │ │ │
│ │ │ │ few tiny. │ │ │
│ │ │ │ G+round diploc. │ │ │
│ │ │ │ Pl. fluid almost│ │ │
│ │ │ │ pure │ │ │
│ │ │ │ pneumo-like, few│ │ │
│ │ │ │ G-forms probably│ │ │
│ │ │ │ the same. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
757│ 16│ 6│ 14│Br. G—B tiny, to │ + │ + │ 0
│ │ │ │ medium. G—like │ │ │
│ │ │ │ M. catarrhalis. │ │ │
│ │ │ │ G+cocci, pairs │ │ │
│ │ │ │ and chains. Few │ │ │
│ │ │ │ B. W. like. │ │ │
│ │ │ │ Lung, many G—B │ │ │
│ │ │ │ like B. I. Some │ │ │
│ │ │ │ cells filled, │ │ │
│ │ │ │ also G—cocci. M.│ │ │
│ │ │ │ catarrhalis like│ │ │
│ │ │ │ and rare B. │ │ │
│ │ │ │ welchii like. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
758│ 16│ 14│ 16│Br. pneumo-like in│ + │ ? │ 0
│ │ │ │ excess. G—B from│ │ │
│ │ │ │ tiny to forms │ │ │
│ │ │ │ stouter than B. │ │ │
│ │ │ │ I. Few strept. │ │ │
│ │ │ │ rare M. │ │ │
│ │ │ │ catarrhalis. │ │ │
│ │ │ │ Lung, │ │ │
│ │ │ │ pneumo-like. │ │ │
│ │ │ │ Phago. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
761│ 17│ 7│ 19│Br. pneumo-like. │ + │ – │ 0
│ │ │ │ B. I. like │ │ │
│ │ │ │ common, M. │ │ │
│ │ │ │ catarrhalis │ │ │
│ │ │ │ like. Both B.I. │ │ │
│ │ │ │ and M. │ │ │
│ │ │ │ catarrhalis │ │ │
│ │ │ │ phagocyted. B.I.│ │ │
│ │ │ │ single or in │ │ │
│ │ │ │ threads. Some │ │ │
│ │ │ │ typical groups. │ │ │
│ │ │ │ Lung, pneumo, │ │ │
│ │ │ │ caps, rare, M. │ │ │
│ │ │ │ catarrhalis │ │ │
│ │ │ │ like. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
762│ 17│ 10│ 12│Br. numerous B.l. │ + │ + │ +
│ │ │ │ like typical, │ │ │
│ │ │ │ also many │ │ │
│ │ │ │ pneumo. and M. │ │ │
│ │ │ │ catarrh. Lung │ │ │
│ │ │ │ same. M. │ │ │
│ │ │ │ catarrh. │ │ │
│ │ │ │ phagocyted. B.I.│ │ │
│ │ │ │ smear, many │ │ │
│ │ │ │ phagocyted, many│ │ │
│ │ │ │ pneumo. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
763│ 17│ 11│ 13│Lung, pneumo-like,│ 0 │ – │ –
│ │ │ │ slight │ │ │
│ │ │ │ phagocytosis. │ │ │
│ │ │ │ Pl. fl., pneumo │ │ │
│ │ │ │ and few strept.,│ │ │
│ │ │ │ slight │ │ │
│ │ │ │ phagocytosis. │ │ │
│ │ │ │ │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
764│ 17│ 9│ 6│Br. B.I. smear. │ + │ 0 │ 0
│ │ │ │ Cells crowded. │ │ │
│ │ │ │ Pneumo-like │ │ │
│ │ │ │ fewer, │ │ │
│ │ │ │ occasional │ │ │
│ │ │ │ G—stouter │ │ │
│ │ │ │ thread. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
765│ 17│ 9│ 16│Br. pneumo. B.I. │ + │ + │ 0
│ │ │ │ few scattered. │ │ │
│ │ │ │ G+flattened │ │ │
│ │ │ │ diploc. Phago. │ │ │
│ │ │ │ of B.I. and │ │ │
│ │ │ │ pneumo. Lung, │ │ │
│ │ │ │ pneumo-like, │ │ │
│ │ │ │ rare strept. │ │ │
│ │ │ │ very │ │ │
│ │ │ │ questionable G—B│ │ │
│ │ │ │ free and in │ │ │
│ │ │ │ cells. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
767│ 18│ 10│ 14│Br. rather round │ – │ – │ 0
│ │ │ │ pneumo-like with│ │ │
│ │ │ │ caps. B.I. few. │ │ │
│ │ │ │ Scattered, also │ │ │
│ │ │ │ in cells. Lung, │ │ │
│ │ │ │ few bacteria. │ │ │
│ │ │ │ G+strep. often │ │ │
│ │ │ │ phagocyted. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
770│ 19│ 11│ 9│Br. crowded with │ + │ + │ –
│ │ │ │ B.I. like. Few │ │ │
│ │ │ │ G+cocci and │ │ │
│ │ │ │ fewer M. │ │ │
│ │ │ │ catarrh. like. │ │ │
│ │ │ │ Pl. fluid │ │ │
│ │ │ │ G+flattened │ │ │
│ │ │ │ pairs, pus │ │ │
│ │ │ │ cells, │ │ │
│ │ │ │ phagocyted. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
773│ 21│ 20│ 3│Br. few bacteria │ – │ – │ –
│ │Recurrence.│ │ G+and │ │ │
│ │ │ │ G—pneumo-like. │ │ │
│ │ │ │ Rare G+—thread. │ │ │
│ │ │ │ Lung, pneumo and│ │ │
│ │ │ │ rare strept. Pl.│ │ │
│ │ │ │ fluid, │ │ │
│ │ │ │ pneumo-oat │ │ │
│ │ │ │ shapes, etc. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
778│ 24│ 23│ 17│Br. B.I. smear. │ + │ + │ –
│ │ │ │ Fewer large │ │ │
│ │ │ │ pneumo. Lung, G │ │ │
│ │ │ │ + small diploc. │ │ │
│ │ │ │ Few B.I. like. │ │ │
│ │ │ │ Pl. fluid, few │ │ │
│ │ │ │ cells, no │ │ │
│ │ │ │ bacteria. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
781│ 26│ 5│ 4│Br. crowded with │ – │ + │ –
│ │ │ │ staph. like. │ │ │
│ │ │ │ Fewer G—B, │ │ │
│ │ │ │ larger than │ │ │
│ │ │ │ B.I., few M. │ │ │
│ │ │ │ catarrhalis │ │ │
│ │ │ │ like. Lung G+ │ │ │
│ │ │ │ small staph. │ │ │
│ │ │ │ like, caps, │ │ │
│ │ │ │ cocci in pairs │ │ │
│ │ │ │ and chains. Few │ │ │
│ │ │ │ tiny G—B. Pl. │ │ │
│ │ │ │ fluid │ │ │
│ │ │ │ pneumo-like and │ │ │
│ │ │ │ elong. cocci in │ │ │
│ │ │ │ chains │ │ │
│ │ │ │ capsulated. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
782│ 26│ 8│ 3│Br. numerous B.I. │ + │ – │ 0
│ │ │ │ like scattered, │ │ │
│ │ │ │ some phagocyted.│ │ │
│ │ │ │ Fewer G+ flat │ │ │
│ │ │ │ pairs with │ │ │
│ │ │ │ capsule. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
783│ 26│ 8│ 1│Br. G+small caps, │ + │ – │ 0
│ │ │ │ pneumo-like. │ │ │
│ │ │ │ Lung poor smear,│ │ │
│ │ │ │ occasional │ │ │
│ │ │ │ pneumo-like. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
784│ 28│ 8│ 6│Br. capsulated │ + │ + │ 0
│ │ │ │ pneumo-like, few│ │ │
│ │ │ │ strep. Lung, │ │ │
│ │ │ │ chiefly │ │ │
│ │ │ │ pneumo-like. few│ │ │
│ │ │ │ G—B like B.I., │ │ │
│ │ │ │ also │ │ │
│ │ │ │ G—pneumo-like. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
786│ 29│ 4│ 2│Br. G+cocci in │ + │ – │ 0
│ │ │ │ round pairs and │ │ │
│ │ │ │ rather flat │ │ │
│ │ │ │ chains, │ │ │
│ │ │ │ suggested caps. │ │ │
│ │ │ │ Tiny G—B very │ │ │
│ │ │ │ rare. Lung │ │ │
│ │ │ │ streptococci │ │ │
│ │ │ │ flattened, often│ │ │
│ │ │ │ phagocyted. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
787│ 29│ 8│ 2│Br. numerous │ + │ + │ 0
│ │ │ │ pneumo-like, │ │ │
│ │ │ │ bacillary forms.│ │ │
│ │ │ │ A rare │ │ │
│ │ │ │ suspicious B.I. │ │ │
│ │ │ │ like, some of │ │ │
│ │ │ │ these in cells. │ │ │
│ │ │ │ Lung, caps, │ │ │
│ │ │ │ elongated │ │ │
│ │ │ │ diplos, and │ │ │
│ │ │ │ chains of elong.│ │ │
│ │ │ │ cocci. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
791│ Nov.│ 6│ 6│Br. few bacteria. │ + │ + │ –
│ 1│ │ │ G+pneumo-like │ │ │
│ │ │ │ round, G—B and │ │ │
│ │ │ │ threads, size │ │ │
│ │ │ │ varies, like │ │ │
│ │ │ │ B.I. Lung, G + │ │ │
│ │ │ │ caps, pneumo. │ │ │
│ │ │ │ G+Large B. few │ │ │
│ │ │ │ suspicious │ │ │
│ │ │ │ G—coccoid forms.│ │ │
│ │ │ │ Pl. fl. caps, │ │ │
│ │ │ │ pneumo and caps,│ │ │
│ │ │ │ elong. chains. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
792│ 2│ 6│ 3│Br. caps, │ + │ + │ –
│ │ │ │ pneumo-like bac.│ │ │
│ │ │ │ forms and │ │ │
│ │ │ │ chains. G-caps, │ │ │
│ │ │ │ pneumo-like. Few│ │ │
│ │ │ │ G—B. │ │ │
│ │ │ │ questionable. │ │ │
│ │ │ │ Lung. caps, │ │ │
│ │ │ │ pairs and chains│ │ │
│ │ │ │ of elong. cocci,│ │ │
│ │ │ │ in cells. Pl. │ │ │
│ │ │ │ fluid, numerous │ │ │
│ │ │ │ caps, chains of │ │ │
│ │ │ │ diploc. │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
793│ 4│ 10│ 3/2│Br. M. catarrh. │ – │ – │ –
│ │ │ │ and G+cocci, few│ │ │
│ │ │ │ bacteria, few │ │ │
│ │ │ │ G—B. Ear, │ │ │
│ │ │ │ G+cocci. │ │ │
│ │ │ │ │ │ │
───────┼─────┼───────────┼─────┼──────────────────┼───────┼─────┼───────
│ │ │ │ Total │ 20 │ 13 │ 2
│ │ │ │B. influenzæ │ 66½ │ 46 │ 14
│ │ │ │ found—Percentage│ │ │
│ │ │ │ │ ——— │ ——— │ ———
│ │ │ │Total percentage │ │ 78 │%
│ │ │ │ for B. influenzæ│ │ │
───────┴─────┴───────────┴─────┴──────────────────┴───────┴─────┴───────