In my first report I showed that in the throats of persons not known to have been in contact with cases of cerebro-spinal fever organisms were frequently found which were indistinguishable from meningococci isolated from the cerebro-spinal fluid of persons suffering from that disease.

The serological characters of 66 strains of meningococci obtained from the cerebro-spinal fluid in cases of meningitis have been studied. Serological tests of a similar nature have been applied to 86 strains of Gram-negative cocci, culturally identical with meningococci, obtained from the naso-pharynx of non-contacts. The two series have been compared in respect of agglutinability, agglutinogenic capacity, and absorptive capacity with the following results:

The majority of the spinal strains can be divided into two main groups by simple agglutination tests with selected spinal sera: about 27 can be assigned to Group I and 34 to Group II, the remaining five being relatively inagglutinable or equally agglutinated by sera of both groups.

(1) Meningococci from 60 cases of cerebro-spinal fever have been submitted to serological tests and compared with meningococcus-like micro-organisms from the naso-pharynx of 71 normal persons. In these serological tests 19 monovalent anti-meningococcus of known pathogenic origin and eight with strains isolated from the naso-pharynx. The tests comprised careful estimation of the agglutinability of these 131 strains with the 19 different sera and also of the extent to which these strains absorbed and removed the agglutinin from one or more sera.

(2) The simple agglutination reactions effected a rough sub-division of these 131 strains into two groups, Group I and Group II, and indicated that in Group I there was a main group comprising the majority and at least two smaller groups containing a few strains only.

(3) Tests for absorption of agglutinin confirmed this rough subdivision into two groups and distinguished with much greater precision the different main groups and smaller groups. In general, each of these groups was found to differ in that they did not absorb the agglutinin for members of the others, and members of each produced sera from which members of the others similarly failed to absorb agglutinin.

(4) Two of the smaller groups, however, represent two “scrap-heaps” of strains unidentified by absorption reactions but suggesting by their agglutination reactions that they belonged to Groups I and II respectively. In the former there were placed three strains of cerebro-spinal and one strain of naso-pharyngeal origin, and in the latter four strains of the former origin and thirteen strains of the latter.

(5) The other main groups and smaller groups contained representatives of both cerebro-spinal and non-contact naso-pharyngeal strains, though not in equal numbers: in the main group of Group I there were placed 24 spinal strains and only one non-contact naso-pharyngeal; in the main group of Group II there were placed 16 spinal strains and 40 naso-pharyngeal, of which 23 were from non-contacts and 13 from contacts.

(6) Variations in agglutinability and absorptive capacity were shown to be so great as to interfere seriously with the use of serological tests for identifying meningococci in practice.

(7) An additional difficulty affecting both the identification of meningococcin and their classification into types or groups and sub-groups is that, even with seven sera, each corresponding to a different group, strains were found, both spinal and naso-pharyngeal, which failed to react typically with any and therefore could neither be ascribed to a particular type or group nor be identified on serological grounds with the other pathogenic strains.

(8) Hence it was concluded (a) that it is impossible to regard these types or groups as representing distinct classes limited by hard and fast lines, and (b) that it is unsafe to exclude any strain from possible pathogenicity on the ground of its failure to agree serologically with any of such sets of sera as are likely to be available in practice, since even the large series I employed failed to include all pathogenic strains.

(9) The conclusion in my first report is therefore maintained that any strain possessing the admitted morphological and cultural characters of the meningococcus should be regarded as potentially pathogenic without considering its serological reactions.

(10) I have found, however, that the strains obtained from the majority of carriers show by absorption tests complete serological identity with known pathogenic strains. To this criterion 58 of my 71 naso-pharyngeal strains conform. These were distributed as follows: 16 out of 138 out-patients attending Lambeth Infirmary in June and July, 1915 (11·6 per cent.); 12 out of 57 non-contact soldiers in February, March and May, 1916 (21 per cent.); 13 out of 24 soldiers in March, 1916, who had had no direct connection with cerebro-spinal fever but in whose neighbourhood two cases had occurred (54 per cent.); 17 out of 62 soldiers who had been in direct contact with cases of the disease (27 per cent.).

(11) Inclusion of those persons who were found to be carrying strains not fully identified serologically did not raise the percentage of carriers to a significant extent.

1. In two areas in the Eastern Counties, Cambridge and Norwich, naso-pharyngeal swabs were taken from 400 individuals, who represented different conditions of health and social circumstances.

The investigation was made at Cambridge between the months of June and October, 1916, and at Norwich during August, 1916.

Owing to the low incidence of cerebro-spinal fever in the two towns during the year 1916 (see p. 249), the general population may be regarded as practically “non-contact” in respect of this disease.

2. As a result of the investigation, strains giving all the cultural and microscopical tests of the meningococcus were obtained as follows:

(a) From 200 swabs taken at Addenbrooke's Hospital during June and July, 1917, mostly from normal people, 30 strains.

(b) From 100 swabs taken at the Norfolk and Norwich Hospital during August, from individuals mostly in impaired health, 27 strains.

(c) From 100 swabs taken in Cambridge during October, from factory employees, who were all in good health and mostly in comfortable circumstances, 37 strains.

3. Such strains were found more often in males of every age group than in females, and in adults more often than in children.

In regard to the influence of health and surroundings, the results of the investigation grouped together show a larger proportion amongst town dwellers than amongst country people and amongst people with impaired health than amongst the healthy.

General conclusions cannot, however, be drawn from these figures because conditions were not always comparable. For instance, the majority of country people were examined in June and July, when positive findings were low.

In examining the employees at a factory, I obtained the strains in a higher proportion from the men working in those shops where air space was more restricted and ventilation less perfectly effected.

4. The 94 strains collected from 400 naso-pharyngeal swabs were tested as regards their agglutinability against certain monovalent sera. These sera were prepared from seven strains of meningococci of cerebrospinal orgin, and from two of the naso-pharyngeal cocci which had been isolated during the course of the investigation. The meningococcal strains used for preparing the sera included strains which had been found identical with others occurring with considerable frequency in cerebrospinal fluid and capable of being grouped in two main groups; they also included strains which differed from these and were apparently rarer; but there is no reason to assume that every variety occurring in the specific disease was represented.

The results of the tests on the above 94 strains may be classified as follows:

(a) 22 gave no agglutination above 1: 100 with any of the sera used.

(b) Two agglutinated well with certain sera, but also agglutinated with normal rabbit serum.

(c) 31 agglutinated up to 1–200 or 1–400 with the sera of a certain group (M I–M IV), and in some instances gave similar agglutination with other sera not belonging to this group.

(d) 39 agglutinated with the sera of the group M I–M IV to the full titre of the homologous strains, while with the sera belonging to other groups good agglutination was not often obtained.

This last group of 39 strains (41 per cent. of all tested) appears to be indistinguishable by simple agglutination tests from the M I–M IV group of cerebro-spinal meningococci. The previous group of 31 (33 per cent. of all tested) shows evidence of serological relationship with meningococci of cerebro-spinal origin, but it is not possible on their agglutination tests alone to give an opinion as to their identity with any meningococcal group.

Agglutination tests as a whole indicated that about 74 per cent. of strains collected on account of their resemblance to the meningococcus in culture, gave evidence of relationship to the meningococcus in virtue of their agglutination reactions with anti-meningococcal sera.

5. In order to determine if the absorption test would corroborate the relationship shown by agglutination, absorption tests were done against a serum prepared by inoculation of a cerebro-spinal strain of meningococcus, M I, with all the strains, culturally and by simple agglutination indistinguishable from pathogenic meningococci, which had been collected from the last 100 swabs (normal factory employees, Cambridge). Nine absorbed the agglutinin as well as the homologous coccus and four absorbed it partially.

Therefore, out of 100 normal people who had not been in contact with a case of cerebro-spinal fever, 9 per cent. were shown to be harbouring organisms in their naso-pharynx which were serologically identical with meningococci of pathological origin (cerebro-spinal fluid) and, in addition, 4 per cent., making 13 per cent. in all, were so closely allied as to be doubtfully distinguishable even by the test for absorption of agglutinin.

Similar results were obtained with strains obtained from Norwich.

The above results were confirmed by testing absorption by these cocci from another serum prepared with another spinal strain of meningococcus possessing properties almost identical with M I. I have not investigated absorption with sera prepared with strains which differ serologically from M I.

6. With regard to those naso-pharyngeal strains which were not identified with cerebro-spinal strains by serological tests (agglutination and absorption), I consider that in view of the great variation in the serological reactions shown by different strains of undoubted meningococci and even by different emulsions of the same strain, it is very difficult, if not impossible, to exclude any such microscopically and culturally typical organisms from the meningococcus group on the basis of serological tests.

(1) An unusual strain of meningococcus has been isolated which produces minute “dew drop” colonies. This character has persisted throughout a large number of successive generations. Every culture, however, has shown lateral off-shoots consisting of colonies which have the size and appearance of those of typical meningococci. In subsequent subcultivations from these colonies the newly acquired size and appearance remain constant.

(2) It is suggested that the strain isolated is a retrograde variety and that the off-shoots are produced by degressive evolution.

(3) It is also suggested that the character which reappears in the degressive step is that of producing a substance beneficial for growth.

It is impossible, however, to offer any satisfactory explanation of the phenomena observed without a more extended series of experiments. This was impracticable at the time owing to pressure of routine work and further observations on the same organism have now become impossible owing to the fact that the small growing strain has died out. Nevertheless the findings seem worth recording in their present state in the hope that they may be of use to others who have met or may meet with similar peculiarities in the course of their work.

During the years 1903 and 1904 while engaged upon an investigation of the micro-organisms present in saliva, I had frequent occasion to make a quantitative bacteriological examination of this material. The object then in view was to define the bacteria that are most numerous in the mouth, so as to see if they could be applied to detect particulate pollution of air by material derived from the upper respiratory passages in a way similar to that in which B. coli is used to detect and measure excremental pollution of water. While certain streptocoeci were found to provide the index in question, particularly S. salivarius (which is constantly present to the extent of 10 to 100 millions per cubic centimetre of normal saliva) it was observed that among other bacteria present in the cultures were certain gram-negative cocci which frequently exceeded 100,000 per c.c. of the saliva of normal individuals.

At the present time owing to the difficulties arising from was conditions, and the stress of work due to the special circumstances in which the study of bacteriology is being prosecuted, we have had in some cases to modify established methods of bacteriological procedure and introduce new technique.

(1) There were nineteen cases and eight deaths at the depot during the epidemic.

One doubtful case during this period recovered, and a sporadic case in June due to Type I also recovered; these are not included in the above, nor is one man who went on leave to Blackpool, and developed the disease (Type II) on arrival.

(2) So far the reserve battalions have had three cases only, with two deaths, although a high carrier-rate wave has been detected in two.

(3) All the cases (except the June case) at the depot occurred during exceptionally cold weather. In the chart the cases appear to lie in thetrough of a great depression of the curve of mean weekly temperature (broken line). They also follow immediately upon exceptional crowding (black line).

(4) There was a well-marked premonitory rise in the carrier-rate in December 1916, before the first case occurred, and an enormous rise before the epidemic was really established.The carrier-rate, which was 19·25% on December 23rd, reache dwhat is usually considered the danger point of 20% (see War OfficeMemorandum on Cerebro-spinal Fever, page 2) just six days before the first case occurred.

It would appear that estimations of the carrier-rate by means of large sample swabbings afford a reliable warning of the imminence or danger of an epidemic.

(5) The cases in the epidemic were nearly all due to the meningococcus of Type II, the organism present in the outbreak of 1916.

The rise in the carrier-rate was also chiefly due to the increase ofcarriers of this type. Freshly joined recruits showed few carriers at all and very few Type II carriers when swabbed before having slept in the barracks.

(6) During the epidemic, the carrier-rate among non-contacts was substantially the same as amongst the actual contacts of cases, averaging34% for the period, in each case.

(7) The proportion of agglutinable strains to inagglutinable strains of organisms morphologically indistinguishable from the meningococcus increased very markedly during the epidemic period.

(8) The treatment of the whole population by the steam zinc sulphate solution spray (which was carried out daily for two seven-day periods with an interval of a fortnight), was followed by a satisfactory drop in the carrier-rate, and by a temporary cessation of cases on each occasion.

(9) 60% of the actual patients suffering from the disease were in their first month of service.

40% of the patients had either been inoculated or vaccinated within seven days of onset (three on the same day); 60% within afortnight.

(10) Previous and concurrent epidemics of German measles, influenza and bronchitis had helped (by causing coughing and sneezing and by lowering vitality) to produce the great rise in the carrier-rate, which culminated in the case epidemic.