1916.
PUBLIC HEALTH.
EPIDEMIC CEREBRO-SPINAL MENINGITIS. FROM A CORRESPONDENT.
the approach of the summer, WI T H cerebro-spinal fever season' may
the be said to be drawing to a close. As the result of the increased prevalence during the past two years, considerable attention has been directed to the disease. Two reports have beerf issued on the subject recently, one b y a special advisory committee of the Medical Research Committee, the second b y the Local Government Board. Read in conjunction these afford much valuable information. The report of the Medical Research Committee summarises in admirable fashion the many reports received from those in charge of the laboratories in various military areas of the country. The Local Government Board report contains a valuable summary b y Dr. Bruce Low on the prevalence and distribution of cerebro-spinal fever during recent years, a preliminary report b y Dr. R. J. Reece on the epidemie prevalence of the disease in England and Wales during the first six months of 1915, and: reports b y Drs. Eastwood, Griffith, and Scott upon the recent researches made in connection with the disease in the laboratories of the BOard; The increased prevalence of the disease m a y be gauged from the f i g u r e s given in the preliminary m e m o r a n d u m bf the L o c a l Government Board Reports. In I913, the number of cases notified was 305; in 1914 , 315 ; in I9I 5 civilian cases alone totalled 2,565. The civilian epidemic, as shown b y the curve given in the Local Government Board Reports, began in the middle of December and reached its height in the last week in April. The military epidemic reached its maximum earlier, about the middle o f March. Both gradually died away during the summer , to make a re-appearance in the l a t e autumn. This year the disease appears to be following approximately a similar course. • This suggests that cerebro-spinal fever is essentially a " contact " disease; it increases in winter and early spring, when the prevailing cold drives people indoors into more intimate contact with one another, and frequently into confined spaces and stuffy atmospheres. It fades away in summer and early autumn, when people seek the open air, and come far less intimately into contact with one another.
207
The disease m a y vary in form from that of a mild type somewhat resembling influenza, to a very severe fulminant type fatal in a few hours. All the evidence goes to show that the disease is caused b y an invasion of the meninges b y the diplococcus intracellularis meningitidis of Weichselbaum. Most recent evidence, to which we shall refer, later shows that there are at least four epidemic types of the meningococcus, a fact which may to some extent account for the varying degrees of virulence of the different epidemics. I t has been suggested that the meningococcus is b u t a form of a pleomorphic organism, and that the ultimate cause of the disease is in reality a filterable virus. It cannot be said, however, that the evidence either of the pleomorphism or of the filterability of the virus is for the moment at all convincing. In regard to the former, the doctrine is deafly at variance with the accumulated evidence of careful observers, and can no more be accepted than could the view of Jaeger several years ago, namely, that a Gram-positive coccus was largely responsible for this disease. In regard to the view that the disease is caused b y a virus which is a filterpasser, we will confine ourselves to one criticism, namely, that the procedure adopted for its demonstration is such as would bring about disintegration of the cocci, and liberate therefrom a fever-producing endotoxin, about the presence of which there has been no doubt for some years past. The disease prevails more among the town dwellers than the country inhabitants. The tables illustrating Dr. Reece's article show that the greatest number of cases among the counties occurred in Lancashire and the West Riding of Yorkshire, where the population is in the main grouped in county-boroughs and urban districts. In Londbn, where the population is wholly urban, the proportion of cases to population ('oi 9 per I,OOO) is more than twice as great as that of Lancashire ('oo8), and nearly four times that of the West Riding ('005). The prevalence of t h e disease is relatively greater among the military than among the civilian popnlat!0n. This is probably on account of the increased contact brought about b y the more crowded hutments, barrack-rooms, and billets. There is now little doubt that the disease is sprea4 b y the distribution of the meningoeoccus from nasopharynx to nasopharynx, although the influences which determine the subsequent invasion of the meninges are still a problem
2o~
PUBLIC HEALTH.
for solution. To say t h a t there is individual predisposition but begs the question, although such a predisposition cannot by any means be denied. There is at present no evidence t h a t certain persons possess a greater i m m u n i t y in the blood than others, although evidence of such immunity is readily detected in those who have suffered from the disease. Cerebrospinal meningitis has been observed frequently to supervene upon German measles, influenza, tonsilitis, and other conditions in which the nasopharynx and throat may be left in an abnormal condition. But this is by no means always the case. As to the exact portal of entry into the nervous system, there is still considerable doubt. In certain cases the entry of the coccus into the blood-stream is undoubted. In other cases it would appear more probable t h a t its entry into the nervous system is through the cribriform plate or through the sphenoidal sinus. That the usual point of entry into the body is the nasopharynx, there appears to be no manner of doubt. We learn on good authority t h a t in thirty-five undoubted cases of cerebro-spinal fever the meningococcus was found in the nasopharynx in all, and was in every case a coccus belonging to known epidemic types. Evidence goes to show the disease is spread mainly by the carrier who, having the organism in his nasopharynx, often suffers little or no inconvenience from its
JlyI,m,
focuses attention upon the Gram-negative cocci of the normal nasopharynx, and raises the question as to what organism is to be regarded as the meningoeoccus. In the nasopharynx there are m a n y Gram-negative cocci, M. catarrhalis, iV[. Flavus I. and II., etc., which by cultural tests can fairly readily be differentiated from the mening0eoccus ; but, as shown by the Local Government Board experts, there are about IO per cent. which cannot be so differentiated culturally. Like the meningococcus, t h e y grow at 37 ° C, and not at 23 ° C, they ferment glucose and not saccharose. Are these to be regarded as meningococei ? Dr. Eastwood and his colleagues for the moment return the answer " Y e s . " Our criticism of such an answer must be t h a t although such cocci are undoubtedly culturally like the meningococeus, m a n y of them have not yet been shown to produce epidemic cerebro-spinal meningitis. In the production of such a meningitis, it is primarily the coccus which can be and has been isolated from the cerebrospinal fluid t h a t counts. Recent investigation has shown t h a t of more than one hundred cocci isolated f r o m the C.-S. fluid in military cases, all belong to one of four types. These types are distinct and when injected in appropriate doses into an animal, produce in it a serum which only agglutinates t h a t coccus and not the allied cocci. Let us make this clear by a diagram.
TABLE showing agglutination results of the e fidemic types of cocci. ~.S.
Type I. Serum.
Type II. Serum.
Type III. Serum.
Type IV. Serum. Remarks.
i/IOO
,/lOO ++
,/400 ++
/lOO
1/4oc ,/lOO 1/2oo 1/4oo
/IO0
++
1/400
++
Type
++
++
++
+
++ ++
++
1/200
++ ++
++
++
++ +
++ --
I. Agglutination
,,
II.
,,
,,
III.
,,
,,
IV.
,,
,,
I.-III.
,,
,,
II.-IV.
,,
N.S. =Normal Serum. + + ~- Complete agglutination. + ~ Partial agglutination. (+) = Slight agglutination. m
presence. The case itself comes early under medical control, and the opportunity for the dissemination of the coccus by it, as compared with t h a t of the carrier, is small. The swabbing of the immediate contacts of a case is therefore a matter of prime importance. By some authorities, however, it is seriously doubted whether such a course is practicable. I t is maintained t h a t the meningococcus occurs in a large percentage of normal people. This
t
From this it will be seen Type I. coccus agglutinates with Type I. Serum; Type II. coccus agglutinates with Type II. Serum, etc. While it is true t h a t this is frequently the case, it should • be stated that some meningococei also frequently show a partial agglutination with Sera of other strains, more particularly Type I. with Type III. Serum, and Type II. with Type IV. Serum. The question next arises, Do cases have the same type of meningoccocus in the nasopharynx
PUBLIC HEALTH.
x916.
as in the cerebro-spinal fluid ? For answer we are privileged to quote the fact that in twenty recent cases, in which this m a t t e r has been investigated, such has been found to be the ease. Moreover, in the 35 cases referred to previously, the coccus isolated from the nasopharynx was in every case one of the epidemic types. Furthermore, the contacts of such cases almost always yield the same epidemic type, as the case with which they have been in contact. In a great number of instances, a history of close contact is given; such as sleeping with, next, or opposite to the case, close attendance upon it, and so forth. We have illustrated the behaviour of the epidemic types of meningococcus to the standard sera. In the following diagram we show the behaviour of the other cocci which culturally resemble the meningoeoceus.
209
I50 carriers of the non-epidemic type were liberated, and no evidence of any case of meningitis has arisen therefrom. On the other hand, among the 12o carriers of cocci of epidemic types, four have subsequently developed the disease. Several cases have come to our knowledge recently in which all the evidence pointed to a certain person as a carrier. Nasopharyngeal cultures have indeed shown that such was the case ; and it is worthy of note t h a t in every instance the coccus isolated from the carrier was one of epidemic type, and the eoeeus from the C.-S. Fluid oL the eases infected was also of the same type. It has been stated that the agglutination test is of but little value. With our recent advance in knowledge, the reason for such a statement is easily seen. If a Type II., III.,
TABLE showing agglutination results on cocci culturally resembling the meningocoecus. H,,, .............
l'~.S.
I/IO0
Type I. Serum.
Type II. Serum.
I/Ioo++ i/2oc++ I/4oo++ i/ic
++
+
(+)
--
:/2o, ~/4c
+q
++
+
(+)
Type III. Serum.
I/!oo++-/TJ
+q
+ +
Rema~s.
~/-~0-oo~i/2oo ~I/4oo + +
+
(+) f -N.S. = Normal ;erum. + + = Complete agglutination.
+ = Partial agglutination.
I t will be seen that some cocci agglutinate with all the sera and with normal serum in addition. These eoeei probably belong to the group which has been termed Flavus III. Other cocci agglutinate with all the sera slightly, showing what may be t e r m e d " g r o u p " agglutination. Others exhibit no agglutination. Such cocci probably represent the socalled pseudo-meningococci, which have been frequently observed by other researchers, English, American, and German. In our opinion they are not meningocoeei. But if one is constrained to call them meningocoeei, then they belong to no type of meningococei which have as yet been demonstrate d in the cerebro-spinal fluid of cases of epidemic meningitis. The agglutination test thus employed shows that of the nasopharyngeal cocci which closely resemble meningococei culturaUy, fully 5o 'per cent. are not of the epidemic type. Thus, of 27o agglutinations made of positive contacts of actual cases of eerebro-spinal fever, only 12o were found to be of epidemic type. The
i
Type IV. Serum.
++
++
++
+
(+)
--
e
Probably ~ . Flavus III. of Lingelshdm " Group "Agglutination Pseudo-l~{eningococcus Agglutination
t
(+) = Slight agglutination.
or IV. coccus be agglutinated against Type I. serum, it will fail to give agglutination, and the test will apparently be valueless. The agglutination test when applied rightly, i.e., against sera of all the epidemic types, is of utmost value. When the test is thus applied to those cocci from the nasopharynx culturally resembling meningococei, the percentage of the meningococcus in the normal throat is approximately two to three per cent. We have laboured this point at some length because it is of primary importance. It shows that the percentage of the meningoeoceus is not so large as is often supposed in the normal population, and that the swabbing of contacts can be successfully applied. In our experience, if applied early and not to immediate contacts only, the spread of the disease can be materially arrested. It is true that the isolation of carriers, especially in civilian life, forms a somewhat awkward problem. Generally speaking, a positive contact carries for about three to five
2io
PUBLIC HEALTH.
weeks, b u t m a y do so for a period up to two years. There appears, however, hope of a more speedy form of treatment. In the outbreak which occurred at Cologne early in 1915, the German authorities found that they could clear their carriers b y placing them in an inhalatorium, the atmosphere of whieh had been impregnated b y a super-heated steam spray (Wassmuth's atonfiser) with a fluid (Sano's) which liberated chlorine. We know of experiments on similar lines now being made in this. country, which have shown that it is possible b y this means to free carriers of the meningococcus, for the time being at any rate. The day m a y not be far off in which it will be the duty of the M.O.I-I. to swab contacts of cases of C.-S. F., and to disinfect the positive contacts in a municipal inhalatorium in much the same way as he now disinfects the dwellings. We propose to give a few hints which, although generally known, are not, in our experience sufficiently realized as being of practical importance. Since for diagnostic purposes it is important that a growth from the cerebro-spinal fluid be obtained, it should be borne in mind that it is imperative that the fluid be kept warm after removal. It is almost useless to attempt growth if the specimen be allowed to cool. Specimens, therefore, sent through the post" are valueless. The same remark also applies to swabs. Swabs must not be allowed to dry, and should, if possible, be plated on the spot. For this purpose waterjacket tins carrying 3½-in. petri plates are convenient. These can be filled with water at 37 ° C., at the time of swabbing, and will keep the plates sufficiently warm until the laboratory is reached. In swabbing the nasopharynx, the utmost care must be taken that no saliva gets upon the swab, otherwise the growth of the meningococcus will be inhibited. It is well therefore to use a curved glass-protected swab, such as West's. In regard to the sterilization of the skin before a lumbar puncture, it is worthy of note that painting with tincture of iodine which is so generally in vogue, does not kill the staphylococcus epidermidis, and contamination of the fluid with this organism frequently occurs. From the bacteriological standpoint, spirit lotion or ether are much to be preferred. For culture purposes, it is essential to use a clear medium so that the character of the growing colonies m a y be observed, The
J~E,
meningoeoccus is not a good grower, and requires medium of a special nature. For primary culture from the nasopharynx, it is well to use a medium containing ascites fluid or serum. '~ Nasgar " is widely known, b u t during the war is difficult to prepare on account of the impossibility of procuring nutrose and W i t t e ' s peptone. It has, moreover, proved disappointing in use. Kutscher's serum agar (placental extract, nutrose, glucose, peptone, and agar) is used in the Local Government Board Laboratory with satisfactory results. The new " Trypagar " medium of the Central C.-S. F. Military Laboratory, also gives highly satisfactory results and is much more readily prepared. It is made with a trypsinised broth of ox-hearts as the base of the agar medium, to which a IO per cent. saline extract of pea-flour is added. For primary culture from cerebro-spinal fluid, it is well to add a little fresh blood upon the surface of the plate. A good method of rapid preparation of an agglutinating serum is given in the December number (I915) of the R.A.M.C. Journal. In conclusion, we summarize the chief points : At present the mass of evidence points to the fact that cerebro-spinal meningitis is produced b y the invasion of the meninges b y the meningococcus, the diplococcus intracellularis of Weichselbaum. Of this coccus there are at present four epidemic types, of which two are predominant. These epidemic types occur in the normal nasopharynx in about 2 to 3 per cent. Other Gram-negative cocci, culturally like the meningococcus~ also occur, giving a much higher percentage. These cocci are not identical with epidemic strains and have not as yet been found to be associated with epidemic meningitis. THE CARNEGIE UNITED KINGDOM TRUST. inquiry which is being made by Dr. E. W. T H EHope into the existing provision for promoting the physical welfare of mothers and infants will provide interesting material, showing what is being done in tbJs country. Notwithstanding the difficulty of filling up the forms which Dr. Hope has issued, owing to deficiency of staff, it is probable that effort will be made to comply with his request, for it may be that the Trust has it in its power to render useful service if it receives sufficient encouragement for this purpose. Under any circumstances, the information is well worth collecting.