It was not my original intention to include the subjects of diagnosis and treatment in this presentation, except in so far as I have already referred to them in the relation of my Manila experiences in the preceding pages. I have decided, however, to add a chapter upon Diagnosis and Treatment, for the sake of completeness. No attempt will be made to present these subjects in the orthodox way.

Rather, my remarks will be confined to such matter as I believe to be thoroughly practical and relevant.

In my opinion, the day has arrived when we may properly exclude from such handbooks as this one (intended for practical guidance), all such methods of diagnosis and treatment as have failed to meet the test of actual experience through a reasonable length of time. Twice in recent years,[17] I have described the diagnosis and treatment of plague, attempting in each case to present a reasonably full account of the methods employed and advocated by authorities, for theoretic reasons and from the recorded personal experiences of medical men throughout the world. There comes a time, however, when wheat and chaff must be separated and when methods which have failed, in application, to justify preformed expectations must be relegated to the department of historical medicine.

[17] Tropical Medicine (1907) and Hare's Modern Treatment (1911), vol. 1.

Judging from recent medical text books it is evident that medical writers are generally accepting this view as the proper one. At any rate, my experiences and those of my medical friends during the Manila epidemic of 1912–1914, have led me to discard as impracticable, unproven, disproven or unpromising, certain plans of treatment formerly deemed worthy of trial. I do not refer to these methods individually but will content myself, instead, with reciting briefly the methods which I believe, from personal experience and the collected experience of others, to be worthy of continuance and of further trial.

Diagnosis.—The rapid diagnosis of plague is always of the utmost importance, both from the view-point of prognosis and treatment, in the individual case, and from the community view-point of the recognition of the presence of a dangerous communicable disease, with the resultant obligation falling upon the health authorities.

The Biologic Diagnosis.—Let us understand, first and finally, that but one diagnosis is absolutely and irrefutably dependable, viz.: the biologic diagnosis. Herein I would include not only the recovery of the pest bacillus from the patient, but the recovery and identification of the organism from inoculated animals, infected from blood, tissues, secretions or cultivated plague bacilli derived from the human patient or cadaver.

This entire process involves a lapse of time of several days, and, while it is indispensable in the earliest cases of an epidemic, and highly desirable for the proper study of all cases of plague, it is impracticable and unnecessary, in communities where plague is known to exist, to carry out more than the first steps of the biologic diagnosis, viz.: the recovery of B. pestis (morphologic identification) from the patient.

Necessity for Trained Bacteriologist.—It is evident that the services of a trained bacteriologist are indispensable in the accurate diagnosis of plague, unless (as rarely is the case) the observer himself is both clinician and bacteriologist. Even in this case it is far better for two persons, clinician and bacteriologist, to work together. I will not discuss the technic of the procedures of biologic diagnosis, which is described by Dr. SchÖbl in the preceding pages. Except under circumstances of necessity, the clinician should always turn this work over to the bacteriologist.

Serum reactions, when present, occur too late to be of service in practical diagnosis.

The necessary procedures of the biologic diagnosis include blood-culture, smear examination (microscopic) of aspirated material from the oedematous tissues surrounding gland masses and from glands themselves; examination of sputum smears and of thick-blood smears.

All should be practised but, according to our Manila experiences, smear examinations of aspirated material and blood cultures are the most reliable methods, in the hands of a competent bacteriologist. Attention is invited to the reports of Dr. Otto SchÖbl, already quoted.

Bacteriologic Procedure.—Dr. SchÖbl was able to secure positive blood cultures, within 24 hours, from all of a long series of cases of plague, both bubonic and septicÆmic. As much blood as it was possible to secure was aspirated from superficial veins and introduced into the culture media at the bedside, ten c.c. being secured whenever it was possible.

The smear preparations for staining and culture inoculations upon slants were also made at the bedside from aspirated matter obtained from oedematous periglandular tissues or from gland puncture, an aspirating syringe being used. The drop or two of fluid which can be expelled from the hollow needle is usually sufficient for smears and tube inoculations.

Non-biologic Diagnosis.—I do not contend that other diagnostic means than biologic ones should not be used in plague.

On the contrary, it will inevitably happen at times that resort must be had to methods of diagnosis which are purely clinical. When this is the case, treatment, along lines to be detailed presently, should be instituted upon the establishment of a presumptive diagnosis. This presumptive diagnosis may be reached after due consideration of physical signs and symptoms. A carefully taken history of the onset and course of the disease will be valuable but unfortunately such histories can rarely be secured. It is far safer to mistakenly pronounce a case "plague" and to institute appropriate treatment, than it is to hesitate in the absence of a perfect clinical picture and to permit the golden moment for treatment to pass.

It must be remembered that septicÆmic, bubonic and pneumonic plague are all manifestations of systemic infection with B. pestis; that they are all expressions of the same disease; that they call for the same treatment and that when the distinctive signs of bubo or pneumonia appear the disease is dangerously advanced.

It should also be realized that every case is, almost from its onset, a septicÆmic case, either mildly or overwhelmingly so. Accordingly the treatment should invariably be the treatment of septicÆmic plague.

The attitude of the diagnostician should be one of suspicion and he should have the courage to carry out antiplague treatment, practically upon suspicion. In this way only can the mortality of plague be greatly reduced. It is true of plague, just as it is true of cholera, that many of the fatal cases develop and become hopeless before the disease is suspected or diagnosticated. It is also true that many fatal cases of plague, in times of epidemic, completely escape recognition during life, the diagnosis being made in the autopsy room.

Therefore, I lay great stress upon the necessity for an attitude of suspicion on the part of practitioners, wherever even a single case of plague (human or rodent) is known to have occurred.

When it becomes necessary to establish a presumptive diagnosis, i.e., without resort to the microscope, the following symptoms and physical signs will be found to be most significant.

Symptomatology.—Acuteness of onset; rapidity of fever development; rapidity of the development of mental dulness or cloudiness, impairment of speech, delirium, stupor or restlessness; early and extreme prostration (perhaps more pronounced than in any other acute disease); extreme tenderness over involved gland masses, in the bubonic type of plague; cough, with considerable frothy sputum, soon becoming blood-discolored, in the pneumonic type of plague; and early cardiac asthenia in all clinical types of plague, septicÆmic, pneumonic and bubonic.The following diseases may be confounded with plague, if symptoms alone are considered: typhus (exanthematicus), influenza pneumonia, broncho-pneumonia, severe malaria, septicÆmia, acute toxic typhoid, venereal bubo, mumps and tonsillitis.

I call attention again to the fact that mild cases of plague, septicÆmic and bubonic, occur at times, clinical pictures in such cases being incomplete.

The statement that the prognosis in all cases of septicÆmic plague is hopeless is not confirmed by my experience.

It should also be remembered that primary pneumonic plague and secondary pneumonia developing in the course of systemic plague are quite different in their significance and mortality, primary pneumonic plague being well nigh invariably fatal.

Pathologic Considerations.—Only the student of plague pathology, who has seen a large number of complete autopsies, can understand how universal is the involvement of organs, glands and tissues in systemic plague and how widespread is the distribution of B. pestis throughout the body, and he will best understand how treatment, to be in the least effective, must be given in the very earliest hours of the disease.

Plague is an exquisitely septicÆmic disease and this fact must never be lost sight of by the therapeutist, who must realize that from the earliest moment of infection all plague is septicÆmic plague.

Treatment, Conditions and Prognosis.—Passing to the subject of treatment let us, first of all, admit that even under the most favorable and approved conditions of treatment the mortality is extremely high. On account of the delay which usually occurs in the recognition of plague,—a delay which in the natural order of things is and must be the rule rather than the exception, because of the rapidity of onset of the disease and the fact that it occurs much more frequently in the lower social classes than elsewhere,—no brilliant results are to be expected from any plan of treatment.

The matter of plague treatment is far from being in the same satisfactory state as the matter of preventive control. I do feel, however, that biologic treatment from the earliest possible moment, with serum, is of the greatest promise, however discouraging the general prognosis may be in plague.Serum Treatment.—Recent writers agree that there is no treatment with curative value except that with antipest serum. To this belief I subscribe assent, as I find it entirely in accord with my experience and that of my colleagues in Manila during 1912–1914.

Holding this view, I can see no reason for repeating here the details of purely symptomatic treatment. Symptomatic treatment has for its object the securing of comfort and of relief from suffering for the patient and is highly proper in its place, remembering always that it is not curative and that if employed alone it is worse than inadequate.

Symptomatic Treatment.—Opiates (morphine by needle) for pain, delirium and excitement; application of ice bags and cold or tepid sponge bathing for high temperature; stimulants for heart weakness, are all indicated and are required in nearly every case of plague.

As a rule surgery is not called for nor appropriate, except in cases which develop secondary surgical conditions, which conditions we need not consider at this time.

Statistical Studies in Mortality.—The statistical study of plague mortality from the point of view of treatment is misleading and unsatisfactory for reasons already given in our discussion of treatment, viz.: failure to secure early recognition and early serum treatment, and the greater incidence of plague in the lower social classes.

Few statistical compilations divide the cases studied into moribund and non-moribund, and indeed such division, being a matter of judgment, largely involves the personal equation of the observer.

The ease with which statistics may be moulded to support theories, or to break them down, all with perfect honesty of purpose, is proverbial.

To me, the spectacle of a single case of plague, apparently ill unto death, recovering under the administration of antiplague serum, is more impressive than the contemplation of statistics; and I have seen more than one such case respond to serum treatment and recover.

So far as it goes, however, the study of statistics supports the view that treatment with antiplague serum is effective.

I have not at hand the records of the last 20 or more cases, but of the first 68 cases of plague in the recent Manila epidemic, 32 were either found dead or died upon the same day that they were found.

If we exclude these cases from consideration there remain 36 cases. All of these patients received serum treatment and ten of them recovered.

It is at once apparent that this percentage of recoveries (27 per cent. plus) is far more favorable than the actual percentage of recovery in the series in which cases found dead and moribund are considered, the recovery percentage here being a little more than 14 per cent. It is also quite fair, it seems to me, to make this separation of cases, or even a more liberal one, if we are to consider the effects of serum treatment statistically.

Dosage and Technique of Serum Administration.—The amount of antiplague serum to be given will vary somewhat with the age and weight of the patient and with the apparent severity of the case.

In general terms it may be said that adults should be given from 300 c.c. to 500 c.c. of serum by injection, 100 c.c. being given every four hours. The injection may be either intramuscular or intravenous.

In view of the improvements in technic of intravenous administrations and its comparative simplicity, and especially in view of the uncertainties and delays of absorption from the tissues, the intravenous route should be given the preference. The serum may be delivered intravenously from a large glass syringe, the introduction being very slowly made, or through a gravity apparatus, as in the administration of salvarsan. The serum should not be diluted.

The use of antiplague serum for protective (immunizing) purposes is also recommended—especially when exposure to infection has occurred—in the same way in which diphtheria antitoxin is used. Its protective properties are conceded to be somewhat superior to those of plague vaccines as the protection conferred is immediate, whereas plague vaccines do not protect until sometime after their administration. The dose is from 30 c.c. to 50 c.c.

Prophylactic Serum and Anaphylaxis.—On one occasion in Manila in 1913, when some 30 persons were given prophylactic doses of serum, intramuscularly, following a particularly dangerous exposure to fleas from rats dead from plague, there occurred a number of cases of "serum sickness" (anaphylaxis). These persons suffered from severe urticarial, arthralgic and nervous symptoms, lasting for several days and a few were obliged to enter a hospital. In one case the symptoms did not entirely abate for a week. It has been stated that newly-prepared serum is particularly apt to produce serum sickness when used for immunizing purposes. This form of protection is brief (1 to 2 weeks) and is best suited for use where there has been special exposure.

Plague Vaccines.—Haffkine originally proposed prophylactic immunization, using killed broth cultures of B. pestis (carbolized to ½ per cent.), giving two injections at intervals of 10 days. Statistically it seems to be shown that this prophylactic immunization with dead bacteria reduces the incidence and mortality one-fourth or one-half (approximately). Experimentally, also, it appears that antibodies (agglutinins) are produced by the vaccine (and modifications thereof). Instead of broth cultures, normal salt solution suspensions of killed pest bacilli are usually used in vaccines at present.Castellani[18] has prepared a combined cholera and plague vaccine for use in countries where both diseases coincidentally prevail. It is a mixed vaccine, so prepared that 1 c.c. of the emulsion contains 1000 millions of plague bacilli and 2000 millions of cholera vibrios. The cultures are grown on agar, killed by phenol and suspended in normal salt solution.

[18] A. Castellani: Journal of Ceylon Branch of British Medical Association, June, 1914.

He finds (1) that inoculation of the vaccine in the lower animals induces a production of protective substances for the plague bacillus and the cholera vibrio; (2) that the inoculation of human beings is harmless (producing less reaction than the Haffkine inoculation); (3) that a small amount of agglutinins, both for plague and cholera, appear in the blood of most inoculated persons (similar to amounts produced by Haffkine's vaccine), a rough index only of the amount of immunity produced.