chances of the meningococcus attacking the meninges with success. Secondly, by shortening the' distance between man and man, over- crowding facilitates the transmission of infections of the upper respiratory passages, since these arc present in droplets of secre- tion which are liable to be sprayed out into the surrounding air, in the acts of coughing, sneezing and loud speaking. For this reason, overcrowding favours the occurrence of catarrhal diseases, which so frequently precede and accompany an outbreak of cerebro-spinal fever. Thirdly, for a similar reason, overcrowding tends to produce a high carrier-rate of the meningococcus in a community; thus ensuring to any susceptible individual, freshly introduced, a massive dosage of the organism.
In addition, the rapid transmission from one temporary carrier to another which a high carrier-rate implies may very probably tend to increase the virulence of a strain of meningococcus previously of Jow virulence.
Glover's work on carrier-rates demonstrated that the meningococ- cus carrier-rate is a direct index of the degree of overcrowding, and that, when this overcrowding is remedied by increasing the distance between the beds, a high carrier-rate rapidly falls to a normal rate. There is a sharp rise in the carrier-rate of a community before an epidemic, that is to say, a " carrier epidemic " precedes and accom- panies the " case epidemic." For practical purposes, a carrier-rate of 20 % has been regarded as the danger line.
Cerebro-spinal fever is an acute infectious disease, due to the meningococcus. It occurs sporadically and in epidemics, and has usually as its chief manifestation an acute meningitis affecting both brain and spinal cord. The causal organism is undoubtedly the diplococcus intracellularis of Weichselbaum, a gram-negative coccus of characteristic kidney shape, almost invariably seen in pairs, and having no well-defined capsule. In the body fluids, and especially in the cerebro-spinal fluid, it is usually seen inside a polymorphonuclear white corpuscle. Often, however, the diplococcus is seen to be extracellular. Prognosis in a case is usually considered to be better when a slide of the cerebro-spinal fluid shows the majority of the diplococci intracellular rather than extracellular.
The meningococcus stains well, and is invariably gram-negative. An excellent culture medium is Gordon's trypagar enriched for primary culture with a solution of laked rabbit blood or fresh human blood. The optimum temperature is 37 C. The meningococcus ferments glucose and maltose, but not levulose or saccharose. Whilst it can be distinguished from other gram-negative diplococci by cul- tural tests, the best criterion for identification is serqlogical, that is by agglutination tests with the sera of animals, immunized by repeated injections of killed meningococci obtained by culture from the cerebro-spinal fluid of patients suffering from the disease.
By the use of this method of agglutination and the allied method of absorption, Gordon divided the meningococci found in military cases of the disease in 1915 into four types. Dppter had previously differentiated two types, which he termed meningococcus and para- meningococcus respectively, and the first two types of Gordon, which together account for 80 % of the cases, correspond to Dopter's groups, Gordon's type I being Dopter's meningococcus and his type 2 Dopter's parameningococcus. Gordon's type 3, which is more closely allied to type I than to type 2, gave rise to some 15 % of the cases, whilst Gordon's type 4 was of rare occurrence except in one outbreak at Chatham.
A patient suffering from cerebro-spinal fever harbours only a single type of meningococcus in his cerebro-spinal fluid and it is almost invariably present in his nasopharyngeal secretion.
Determination of the type of the invading meningococcus is of great practical importance, as the serum of an animal immunized against one type has little or no therapeutic or protective value in a patient suffering from an invasion of a different type of meningo- coccus. A therapeutic serum must therefore either be polyvalent or if monovalent, be used only for its appropriate type when the type has been determined. For general use a polyvalent serum has the merit of simplicity and with potent serum the results are ex- traordinarily good.
Tullock has shown that type 2 is a complex type divisible into three sub-groups, and the much greater difficulty in producing a good anti-type 2 serum is probably owing to this fact.
Criticism of Gordon's types has concentrated mainly on his types 3 and 4, but there can be no doubt that Gordon's types were of the utmost value for the epidemic of 1915-8. In a series of 526 strains of meningococci from the cerebro-spinal fluid of patients, 98 % were identifiable with one or other of the four types, and one-fifth belonged to types 3 and 4.
Infection of the nasopharynx probably always takes place first. In most cases a blood infection appears to precede the meningeal invasion, but the actual channel of infection between the naso- pharyngeal secretion and the meninges is uncertain; it may be either through the blood stream, or by the sheaths of the olfactory nerves passing through the cribriform portion of the ethmoid, or by the sphenoidal sinuses.
The incubation period is usually three to four days. The onset is sudden and contrasts with the usually more gradual onset of tuber- culous meningitis. In no disease is early diagnosis of more urgent importance. Intense headache, vomiting, a moderate degree of pyrexia with a comparatively slow pulse, stiffness of the muscles of the neck and a positive Kernig's sign are the primary symptoms. The disease is usually well defined; these five symptoms being all present in 85% of cases, and only some 10% of cases are atypical, the most common deviation being a long initial pyrexia.
If there be any suspicion of the disease lumbar puncture should be performed at the earliest possible opportunity for the purposes of both diagnosis and treatment. Retraction of the head is a later symptom and should never be waited for.
The characteristic "spotted" rash is present in a percentage of cases, which varies considerably in different epidemics. Rashes appear more constant in American experience. In 1917 in London it was present in about 25 % of patients: it is a macular rash appear- ing first on the skin and the dorsum of the foot, then upon pressure points, elbows, buttocks and back. Large purpuric patches are characteristic of fulminating cases, which form about 5 % of the cases. Petechial maculae, erythema, rose spots, and blotches often occur in cases of ordinary severity.
Labial herpes is a later symptom than the rashes, and is of favour- able import. Inequality of the pupils is less common than in tuber- culous meningitis. Squint is seen in a smaller proportion of cases (6%) than in tuberculous meningitis. Hemiplegia, usually tran- sient, and nerve deafness, usually permanent, each occur in about 5% of cases. Albuminuria is common, but usually transient; hae- maturia occurs in a small proportion, and, to a less extent, glycosuria. Constipation is almost invariable and with the incessant vomiting may lead to the diagnosis of an acute abdominal condition.
In children the disease is often ushered in by convulsions. Retrac- tion occurs at a_n earlier stage than in adults. Persistent tetany of hands and feet is common and rapid emaciation occurs.
Three main clinical types of the disease are described, fulminant, severe and atypical. A fulminant case is one in which the initial systemic invasion results in so profound a toxaemia that the death or early collapse of the patient may obscure the meningeal condi- tion. Death may take place in a few hours after onset. Fulminant cases amount to some 5 % and are more common at the height of an epidemic. Typical severe cases form some 85 % of all cases and in them cerebro-spinal fever forms as clear a clinical feature as does any disease. Atypical cases form some 10% and the most usual form is one with a long preliminary pyrexia which may be diagnosed as enteric or trench fever. Ambulant or slight attacks do not occur.
The essentials of the treatment of cerebro-spinal fever are three :
First, early and repeated relief of pressure by lumbar puncture; this procedure alone will considerably reduce the case mortality rate in adults. Secondly, the early and repeated intrathecal admin- istration of a potent antimeningococcal serum (intravenous admin- istration may also be beneficial if the systemic invasion be marked). Thirdly, the relief of pain.
Serum treatment depends for its success upon early administra- tion, upon sufficient dosage and upon the therapeutic potency of the serum itself. The serum treatment of cerebro-spinal fever was intro- duced by Flexner and Jobling in the New York epidemic of 1905 with great success, and reduced the " untreated case" death-rate of over 70% to a "treated case" death-rate of under 20% in those patients who received serum in the first week of illness.
Unfortunately, at the beginning of the 1915 epidemic in England the only serum available proved very disappointing. It had been made from laboratory strains from previous epidemics, and had very little therapeutic effect. Subsequently it was found to fail to agglutinate types I and 2 at a dilution of I in 50. Following the collection of fresh strains from the current epidemic by Arkwright, Gordon, and others, however, a very potent serum was produced from them by McConkey at the Lister Institute in 1916, which again fully vindicated the value of serum treatment, reducing the mortality rate in cases where it was used in the first week to 14%. Gordon has shown that the therapeutic value of serum appears to depend chiefly upon its capacity of neutralizing the toxin of the meningococcus. There is great variation in therapeutic value even in batches produced by the same laboratory, although Gordon's modification of Besredka's method for determining anti-endptoxic content promises well as a method whereby a standardization of anti-meningococcal serum could be reached.
Owing to the complex character of type 2, it is harder to produce a serum satisfactory for all cases infected with this type than to pro- duce potent serum for the other types. The monovalent type I serum produced by Griffith for the Medical Research Committee was extraordinarily effective for type I cases, but his type 2 serum was much less efficacious for type 2 cases.
Lumbar puncture, preferably under an anaesthetic, should be done at the earliest possible occasion. As much cerebro-spinal fluid, usually about 60 c.c., as will flow should be allowed to run from the needle into sterilized test tubes for culture and examination, until the fluid comes one drop at a time with each respiration. If the cerebro-spinal fluid be cloudy or purulent, 30 c.c. of serum warmed to blood-heat is then run in through the needle by gravitation with a rubber tube. The foot of the bed is raised after administration.
