1. In 19 out of 100 experiments guinea-pigs allowed to run free in houses which were presumably plague infected developed the disease and died.

2. On three occasions, namely, on every occasion on which the experiment was made, fleas transferred from plague-infected rats found in houses infected fresh guinea-pigs in the laboratory.

3. Rat fleas, caught on guinea-pigs in plague houses and transferred to fresh guinea-pigs, transmitted the disease in 35% of the cases.

4. A census of rat fleas in houses in Bombay, which were proved plague infected, indicated that rat fleas were 12 times as numerous as in control houses; and that in presumably infected houses rat fleas were four times as numerous as in control houses.

5. In 41 out of 130 fleas taken on guinea-pigs in plague-infected houses, bacilli microscopically indistinguishable from plague were found in the stomach.

6. In the case of 24 of the 27 houses definitely proved to be plague infected, dead rats had been found shortly before the experiments were made.

It must be clear then from the above data on the horse and goat that the inoculation of diphtheria toxin produces a definite leucocytic reaction of polynuclear type. In fact the detailed evidence speaks more clearly in favour of a leucocytic reaction than Besredka's own results on the goat which he immunised. The question then arises: How are we to interpret the contradictory conclusions reached by Nicolas and Courmont? Metchnikoff (1905), while referring to the work of these authors in his Immunity in Infectious Diseases, maintains that a slight leucocytic reaction is apparent from their own figures and especially from the figures obtained in the early hours succeeding an injection. Of course, Nicolas and Courmont considered these slight changes to be negligible.

It seems to me, that the reason must be sought in the method of immunisation employed.

Nicolas and Courmont immunised their animals with very small doses many times repeated, and by such a method it was doubtless possible to reduce local swelling to a minimum. With no local reaction it would seem quite reasonable to expect an absence of general leucocytic reaction, but, as Metchnikoff maintains, such local tumefaction is never absent in horses which are subjected to increasing doses of toxin and which ultimately develop high grade antitoxin.

Throughout the immunisation of the animals detailed in the foregoing paper local swelling and oedema invariably followed the injections except in the earlier stages of immunisation when small doses were being given.

There is no doubt that, in order to produce a high degree of immunity in an animal, the stimulation must be sufficient. A certain small degree of immunity may always be reached without much leucocytic change, as was apparent in the early stages of “Plug's” immunisation.

It must be admitted, however, that, though the leucocytic reaction may be extremely marked after large doses of toxin, it does not necessarily follow that the antitoxin development will be correspondingly influenced.

Such a phenomenon was apparent in the case of "Plug," a relatively refractory horse.

In the more responsive horses, a parallelism between leucocytic reaction after large doses and increased antitoxin development would certainly be expected, without, however, inferring a causal relationship between these two phenomena. We cannot therefore admit the general applicability of Nicolas and Courmont's views, which merely indicate that cells subjected to small oft-repeated doses lose their power of reaction.

On the other hand there is probably no justification for the criticism brought forward by Besredka with regard to the results of Nicolas and Courmont, viz. that in the absence of antitoxin development, an absence of leucocytic reaction was to be expected.

We may therefore conclude that the leucocytic reaction of polynuclear type which follows the injection of large and increasing doses of diphtheria toxin is merely an evidence of efficient cellstimulation and may not necessarily be accompanied by increased antitoxin development.

1. The high estimate formed by Böhme of the utility of this test has been fully confirmed.

2. Other substances, such as skatole-carboxylic acid, which tended to confuse the results of the older method, do not give an indole-like reaction with this reagent.

3. The test is more delicate, and the time required to ascertain the presence of indole is shortened.

4. The method lends itself to accurate colorimetric quantitative estimations, and the amount of indole present at various stages during the cultivation of certain organisms has been determined.

In a previous paper (vol. vi. p. 486) the physiological anatomy of the mouth parts and alimentary canal of P. cheopis has been described. In the present paper we propose to give a detailed description of the external morphology.

For those who are not familiar with entomological nomenclature it is necessary briefly to detail the general structure of a flea.

The great importance of an exact knowledge of the etiology of malaria has given a remarkable impetus to the study of mosquitoes. It has resulted in the growth, during the last few years, of a very extensive literature relating to these insects, and especially to those of the genus Anopheles, which serve as the alternative and definitive hosts of human malarial parasites. Comparatively few writings, however, deal with their internal anatomy.

(1) The characteristic feature of chronic rat plague as described in the foregoing account is the presence of circumscribed abscesses containing plague bacilli in rats caught alive, the animals usually showing no other lesions nor signs of ill-health. No bacilli were seen on microscopical examination of the heart-blood and of the spleen tissue in any of the rats. The bacilli in the great majority of the cases were virulent.

(2) We have grouped the 45 rats conforming to this description which were found during the year's investigation in the Punjab into two classes, one group including those in which the lesions were situated in the abdominal viscera, and the other group including those in which the abscesses were found in regions occupied by peripheral lymphatic glands.

(3) Lesions of the viscera were found principally in the spleen and in the mesentery, while the submaxillary group are most frequently affected among the lymphatic glands.

(4) The peripheral type was observed chiefly during the decline of the epizootic, while the visceral type predominated in the off-season.

(5) In Bombay, only one chronic plague rat was met with out of 17,000 plague-infected rats. In Kasel, 9% of all the rats which were proved plague infected had the chronic disease, while in Dhand the proportion was as high as 28%. With our present knowledge we can advance no adequate explanation of these facts.

(6) We have no direct evidence that chronic plague, as it occurs in the Punjab villages, possesses any significance in the seasonal recurrence amongst the rats of the infection in an acute form, nor is any evidence available which excludes this possibility.

Ehrlich had not long announced his theory of immunity, when Wassermann and Takaki (1898) published their discovery, that the brain matter of the guinea-pig was capable of neutralising tetanus toxin. This was taken as a demonstration of the existence of Ehrlich's receptors in the cells of the normal brain.

In the foregoing paper (p. 512) relationships have been established between loss of weight in test guinea-pigs and dose of diphtheria toxin injected. In connection with the above, the normal increase of weight during the period of observation, the effect of the animal ceasing to eat, or any change of diet, had to be taken into consideration. The following note records observations on normal increase of weight, with constant and variable diet, on healthy animals.

The basis of this paper is the analysis of the bacteriological examination of the fauces of a series of 1019 patients admitted to hospital as cases of scarlatina and a consideration of their subsequent clinical histories. A practice was made of swabbing the fauces of scarlet fever cases without any selection on their admission to hospital. In all cases one bacteriological examination was made and in a number of the cases the examination was repeated.

We have shown that in the laboratory the rat flea, P. cheopis, will readily bite man. When very numerous it will bite man even in the presence of its natural host. We have been able to keep this species of flea alive for more than three weeks by feeding it on man alone.

In the course of some experiments in godowns which were infested with P. cheopis alone, we have often taken fleas in considerable numbers on the legs of men who have entered the godowns for a short time.

In a building in Bombay, in which there had been a severe rat mortality, proved to be due to plague, we have taken rat fleas in large numbers on the legs of men who entered some of the rooms in this building even for a short time.

We can conclude, therefore, that the rat flea, P. cheopis, under certain circumstances, is attracted by man, and will readily bite and feed on him.

For years we have been vainly striving to find some method of treatment capable of preventing or cutting short the relapses so constantly present in Mediterranean fever. Though certain drugs have for a time seemed successful, their beneficial effects are usually uncertain and transient, so that the treatment of the disease has come to be almost entirely symptomatic. Many germicides have been tried; among these “cyllin” has lately been said to shorten the course of the fever. In my hands this has not been the case. Burney Yeo's chlorine and quinine mixture has here occasionally produced very satisfactory results when given with a rising temperature, apparently cutting short a wave of pyrexia, which from experience we had expected to last ten days or more; but its action is very uncertain.

It has long been well established that during the height of scarlet fever streptococci flourish and become greatly predominant in the pharyngeal and buccal mucus. To quote only a few of the many recorded observations.

The Micrococcus catarrhalis was first isolated by Kirchner (1890) from cases of influenza-like illness. Since then several epidemics of acute catarrh and bronchitis associated with this organism have been recorded.