Meningococcus meningitis

Front matter

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HEALTH SCIENCES LIBRARY i

i i I I

Preface

In the preparation of this volume the aim of the authors has been to present in compact form our present knowledge of meningococcus infection of the meninges. As its purposes are practical and it is intended for the use of students and physicians engaged in clinical work, only so much of technical detail has been included as can be carried out with ordinary laboratory facilities. We have not deemed it expedient to burden the volume with minute and detailed laboratory directions, which can be of interest only to the special worker in this field. The physician at the bedside can avail himself only of those diagnostic and therapeutic means which are supplied to him by the equipment of the ordinary general hospital.

In the preparation of the volume a large number of authorities have been consulted, a number too large to be individually enumerated here. We must, however, acknowledge the invaluable aid received from the perusal of the admirable monographs of Councilman, Mallory and Wright, Goeppert, Busse, Elser and Huntoon, and especially the recently published volume of Netter and Debre.

We have appended bibliographic references at the iv PREFACE

end of nearly every chapter. By a chronologic arrangement, the historical advance in our knowledge of each phase of the subject is shown.

We take pleasure in acknowledging our deep gratitude to Dr. Henry Ivoplik, attending pediatrist to the Mount Sinai Hospital, who has generously permitted us to make extensive use of the valuable clinical material in his wards at the hospital. We are also greatly indebted to Dr. Julius Rudisch, Dr. Alfred Meyer, Dr. Nathan E. Brill, and Dr. Morris Manges, attending physicians at the Mount Sinai Hospital, for permission to use their clinical material.

Dr. H. F. L. Ziegel has kindly prepared the index.

We acknowledge with thanks the valuable assistance given us by Dr. John L. Kantor, interne at Mount Sinai Hospital, in the preparation of statistical matter.

We wish to thank Lea and Febiger for permission to reproduce plates from Dr. Koplik's book.

For the kind encouragement and valuable suggestions we are indebted to our publishers.

Henry Heiman, Samuel Feldstein.

Introduction

This monograph is founded on a study of cases of meningococcus cerebrospinal meningitis which have been treated in my service in the children's wards of the Mount Sinai Hospital, New York, and reflects the methods of study of symptoms, diagnosis, and treatment in vogue there. I have been peculiarly fortunate in that the ages of the patients treated varied from earliest infancy to later childhood. A close study of these pages will show that we have been alive to every advance in pathology, methods of diagnosis, and treatment, and have applied the latter in a manner as to give a very definite idea as to their ultimate value. Though the Flexner serum is a most powerful weapon against this affection when properly applied, much remains to be done to deprive the disease of its terrors. This is particularly true of the infection as we see it in infants of tender age below one year.

The mortality in these patients is still not only high, but the maiming effects of the disease on the integrity of the general nervous system are too apparent. The general physician needs in his daily work every aid to the study of symptoms, their vi INTRODUCTION

differentiation and grouping, and an exposition of the safest methods of diagnosis and treatment. It is the object of such a monograph as this to give this aid and thus accomplish a useful mission.

Henry Koplik, M.D.,

Chief of Service.

New York, October 1, 1913.

Chapter I

Definition; Terminology ; History; Geneva, 1805; Medfield, 1806; First Period, 1805-1830; Second Period, 1837-1850; Third Period, 1854-1875; Fourth Period, 1876-1882; Fifth Period, 1893-1903; Sixth Period, 1904 to Present Time.

Chapter II

History; Staining; Morphology; Cultural Characteristics; Growth on Plates, on Slants, on Blood Agar, Ascitic Broth, Potato, Milk; Conditions Affecting Viability of Meningococcus; Effect of Desiccation; Effect of Light; Effect of Temperature; Effect of Moist Heat; Effect of Disinfectant Solutions; Fermentation of Carbohydrates; Agglutination Reaction; Absorption Tests; Precipitin Reaction; Complement Fixation Reaction; Action of Bile Salts; Peritoneal Reaction; Intravenous Reactions; Pathogenicity; Action on Guinea-pigs, Rabbits, Dogs, Goats, Monkeys; Difference in Strains; Gram-negative Cocci in Nasopharynx; Parameningococcus.

Chapter III

Unusual Features; Small Morbidity Rate, 1-2 per 10,000; Contagiousness, Feeble but Certain ; Instances of Contagion; Contagion in Hospitals; Spread from One Locality to Another; Spread from Army to Civil Population; Geographic Distribution; Seasonal Incidence, viii CONTENTS

Winter and Spring; Age Incidence, Children and Young Adults; Sex Incidence; Race Incidence; Influence of Hygienic Conditions, Overcrowding; Condition of the Patient; Sporadic Cases.

Chapter IV

Meningococcus in Nasopharynx of Patients; Healthy Meningococcus Carriers; Number of Carriers influenced by Period of Epidemic, Season, and Intimacy of Patients; Persistence of Meningococcus in Nasopharynx; Carriers in Individuals not Exposed to Infections; Distribution of the Meningococcus in the Respiratory Tract; Condition of Health of Carriers; Source of Meningococcus in Nasopharynx of Patients; Mode of Contagion; Indirect through Agency of Carriers; High Degree of Receptivity, Low Degree of Susceptibility; Causes of Epidemic Outbreaks; Increase of Virulence, Decrease of Resistance; Mode of Invasion of Meningococcus.

Chapter V

Anatomical Features, Pia, Arachnoid and Dura, Ventricles of Brain, Cisternal; Macroscopic Appearance in Acute Stage; Exudate in Fulminating Cases; Condition of Ventricles; Brain Tissue and Cord; Chronic Stage, Thickening and Adhesions; Condition of Ventricles; Obliteration of Outlets; Brain Tissue and Cord; Microscopic Lesions, Acute Stage; Purulent Infiltration; Cells of Exudate; Lesions in Ventricles; Changes in Cortex; Proliferation of Neuroglia and Connective Tissue; Chronic Stage; Organization of Exudate; Perivascular Nodes in Walls of Ventricles;

CONTENTS ix

Degeneration of Ganglion-cells; Lesions in Cord; Degeneration of Nerve-fibres and Ganglion-cells; Degeneration of Posterior Nerve-roots; Cranial-nerve Lesions; Meningococcus in the Nervous System; Lesions in Other Parts of the Body; Upper Respiratory Tract; Lower Respiratory Tract; Lymph-nodes ; Heart; Gastro-intestinal Tract; Liver; Spleen; Kidneys; Joints; Skin.

CHAPTER VI Clinical Types of Meningococcus Meningitis 97

Ordinary; Malignant; Fulminating; Hyperacute; Mild; Abortive; Intermittent.

CHAPTER VII Meningococcus Meningitis in Infancy 106

Importance; Frequency; Difficulties in Diagnosis; Acute Onset; Slight Rigidity of Neck; Bulging Fontanelle; Macewen Sign; Posterior Basic Meningitis; Causative Organism; Pathologic Anatomy; Clinical Course; Identity with Meningococcus Meningitis.

Chapter VIII

Pathogenesis; Mode of Onset; Temperature; Pulse; Respiration; General Appearance and Attitude; Mental Condition; Ocular Symptoms; Changes in Pupils; Disturbance of Ocular Muscles; Optic Nerve Changes; Sensory Disturbances; Motor Disturbances; Reflexes; Vasomotor and Trophic Disturbances; Rigidity of the Neck; Kernig Sign; Brudzinski Neck and Leg Signs; Opisthotonus; Retraction of Head; Rigidity in other Parts; Fontanelles and Sutures; Macewen Sign; Gastro-intestinal Disturbances; Cutaneous Manifestations, Herpes, Petechia?, Purpura; Urine; Blood; Blood-pressure; Relapses; Convalescence.

x CONTENTS

Chapter IX

Lumbar Puncture; Anatomical Considerations and Landmarks; Apparatus; Technic; Physiology of Cerebrospinal Fluid; Characteristics of Normal Cerebrospinal Fluid; Cerebrospinal Fluid in Meningococcus Meningitis; Macroscopic Appearances; Microscopic Appearances; Cytology; Bacteriology; Chemical Characters; Changes in Cerebrospinal Fluid in the Course of the Disease; Character of Cerebrospinal Fluid in Various Types of the Disease; in Fulminating Type; Mild Type; Abortive Type; Chronic Type.

CHAPTER X Complications of Meningococcus Meningitis 173

Frequency; Nervous; Psychic; Motor; Sensory; Ocular; Conjunctivitis; Conjunctival Hemorrhages; Keratitis; Iridochoroiditis; Orbital Cellulitis; Disturbance of Extrinsic Ocular Muscles; Disturbances of Intrinsic Ocular Muscles; Amaurosis; Aural Complications; Otitis Media; Deafness; Pathologic Anatomy and Pathogenesis; Clinical Course; Visceral Complications; Arthropathy; Respiratory; Cardiac; Digestive; Liver; Geni to-urinary Tract; Skin; Sequelae; Motor; Psychic.

Chapter XI

Pathologic Anatomy and Pathogenesis; Clinical Course; At Onset; After the First Week; in Posterior Basic Meningitis.

CHAPTER XII Diagnosis 207

Based on History, Clinical Course, and Laboratory Examination; Sources of Diagnostic Error; Absence

CONTENTS xi

of Characteristic Symptoms; Prominence of Symptoms; Characteristic of Other Diseases; Apyrexia; Mild Psychic Disturbances; Absence of Characteristic Rigidity and Kernig Sign; Intermittent Temperature; Cutaneous Eruptions; Digestive Disturbances; Arthropathy.

Chapter XVI

History; Serum Treatment; Preparation of Serum; Flexner; Kolle and Wassermann; Jochmann; Dopter; Manner of Therapeutic Action; Bacteriolysins; Bacxii CONTENTS

teriotropins; Anti-endotoxins ; Standardizations of Serum; Basic Principles of Serotherapy; Technic of Serum Administration; Systematic Treatment; intraventricular injections; Technic; Dosage; Results of Serum Treatment; Effect on Mortality; Effect on Symptoms; Effect on Cerebrospinal Fluid; Microscopic; Protein Contents; Cytology; Bacteriology; Relapses; Effect on Duration; Effect on Complications; Sequelae; Serum Disease; Untoward Results; Causes of Failure; Symptomatic Treatment; Lumbar Puncture; Passive Hypersemia (Bier); Hot Baths; Drug Therapy; General Management; Prophylaxis; Prophylactic Vaccination.

ILLUSTRATIONS

PLATES

PAGE

I. Macroscopic Lesions of Convexity of Brain Meningococcus Meningitis 80

II. Side View of Brain Meningococcus Meningitis 81

III. Lesions of Spinal Cord Meningococcus Meningitis, Adult Case. (In

color.) 86

IV. Posterior Basic Meningitis, Child Six Months of Age 110

FIGURES

1. Cerebrospinal Exudate 16

2. Pure Culture of Meningococcus 18 Hours Old 17

3. Pure Culture of Meningococcus 48 Hours Old 17

4. Pure Culture of Meningococcus 72 Hours Old 17

5. Colony of Meningococcus 20

6. Plate Culture of Meningococcus 20

7. Slant Culture of Meningococcus 21

8. Showing Membranes Covering Brain and Location of Cisterna 7S

9. Showing Ventricular System of Brain and Foramina of Fourth Ven-

tricle 80

10. Posterior Basic Meningitis, Age Eleven Months Ill

11. Epidemic Cerebrospinal Meningitis. Ordinary Temperature Curve. . . 121

12. Intermittent Temperature Curve 122

13. Babinski Sign 130

14. 15. Kernig Sign 132

16. Brudzinski Signs 133

17. Anatomical Landmarks for Lumbar Puncture 151

18. Cannula, Guard, Stilette, Conus; Rubber Tubing, Manometer Tube. . 153

19. Kroenig's Lumbar Puncture Apparatus 154

20. Crohn's Apparatus for Estimation of Pressure in Cerebrospinal System. 155

21. Position of Patient with the Needle Introduced into the Cerebrospinal

Canal 156

22. Showing Direction of Needle 157

23. Spinal Veins in a Horizontal Section Viewed from Above. (In color.) 157

2t. Measuring the Pressure 159

25. Estimation of Pressure of Cerebrospinal Fluid by Means of Quincke's

Manometer 158

xiii xiv ILLUSTRATIONS

26. Introduction of Antimeningitis Serum into the Spinal Canal by Means

of Funnel 158

27. Catalepsy Complicating Cerebrospinal Meningitis; Age Six Years. .. . 174

28. Cytology of Epidemic Cerebrospinal and Tuberculous Meningitis 228

29. Apparatus for Administration of Antimeningitis Serum 258

30. Intraventricular Puncture and Injection of Serum in an Infant 272

SI. Direction of Needle for Intraventricular Puncture and Injection of

Serum 272

CHARTS

I. Rise or Fall in the Temperature Apparently Due to Lumbar

Puncture 122

II. Critical Fall in the Temperature Caused by Serum Injections 144

III. Repetition of Lumbar Puncture after an Interval of Five Days to

ward off a Possible Relapse 266

IV. Fever Charts of so-called Fast Cases of Meningococcus Meningitis. . 293

CHAPTER I Introduction

Definition. — Meningococcus meningitis is an infectious, slightly contagious disease, which occurs sporadically and in epidemics, due to the presence, in the meninges of the brain and spinal cord, of the meningococcus (diplococcus intracellularis meningitidis), and characterized by a number of constitutional and local symptoms of great variability and irregularity.

Terminology. — In the extensive literature the disease has received a great number of names, such as spotted fever, spotted typhus, black fever, exanthematic typhus, brain fever, petechial fever, epidemic cephalalgia, and cerebrospinal fever. The term most commonly employed is that of epidemic cerebrospinal meningitis. But its inadequacy becomes evident when we consider the great number of sporadic cases which are seen in all the large cities. The specific nature of the disease having become firmly established, an etiologic designation is the only adequate i 1 and proper term. It includes all forms and excludes none.

It is probable that epidemics of meningitis may also be caused by the pneumococcus and the streptococcus mucosus (Bonome), but it is safe to say that the vast majority of epidemics recorded in the literature have resulted from infection by the meningococcus.

History. — The dim history of this disease begins in the Middle Ages. Many epidemics are mentioned in the literature in which symptoms very suggestive of meningitis were present. But, as autopsies were rarely performed, it is impossible to be certain that the disease was meningitis. They were described under phrenitis, petechial fever, cerebral fever, and epidemic cephalalgia.

The accepted history of meningococcus meningitis begins at Geneva in 1805. The epidemic started in February on the left bank of Lake Geneva, and lasted during March and April. Thirty-three persons died of the disease, but there were no cases of contagion at the hospital, and the commission appointed by the Government did not consider it deserving of being called an epidemic. The disease was described as follows by Vieusseux (quoted from Netter and Debre) :

" It began suddenly with extreme prostration ; the face was drawn ; the pulse feeble, small, and frequent, sometimes it could hardly be felt; hard and bounding in a small number of cases. There was violent headache, especially frontal. Then there appeared precordial pain or vomiting of bilious matter, rigidity of the spine, and convulsions in infants. . . . The body presented livid spots, especially after death, sometimes even during life."

The pathological description was given as follows by Mathey:

" The meningeal vessels were markedly congested. A gelatinous blood-stained fluid covered the whole surface of the brain. There was fluid in the ventricles. The choroid plexus was a deep red. A yellow puriform exudate was seen on the posterior aspect of the cerebral lobes and in the interior. There was no manifest change in the cerebral tissue. The same exudate was found along the optic nerves, the base of the cerebellum, and the vertebral canal."

In the United States the disease was first seen in epidemic form in Medfield, Mass., during March, 1806. It was described by Danielson and Mann in a contribution to the Medical and Agricultural Register, bearing the title, " A Singular and Very Fatal Disease which Lately made its Appearance in Medfield, Mass." On account of the remarkable description of the disease given by these authors, a part of the paper is worth quoting:

" Without any apparent predisposition, the patient is suddenly taken with violent pain in the head and stomach, succeeded by cold chills and followed by nausea and vomiting; matter discharged from stomach of no unusual or morbid appearance; respiration short and laborious . . . the eyes have a wild vacant stare without much, if any, appearance of inflammation . . . these symptoms are accompanied by a peculiar fearfulness, as if in danger of falling from the bed or the nurse's arms, and continue from six to nine hours, when coma commences, with increasing debility ; extremities become cold ; livid spots resembling petechia? appear under the skin, on the face, neck, and extremities; pulse small, irregular, and unequal; spasms occur at intervals, which increase in violence and frequency in proportion as the force of the circulation decreases ; at this time the eyes appear glassy, and the size of the pupils varies suddenly, from almost obliterating the iris down to the size of a millet-seed, and then again as suddenly dilating. These symptoms seem to mark the second period of the disease and continue from three to five hours. The third and last stage is distinguished by a total loss of pulsation at the wrists; livid appearances become more general; spasms more violent;

coma more profound; death! The patient has, in general, continued in the last stage from six to twelve hours."

On post-mortem examination, serous effusion was found between the membranes, which adhered to each other and to the brain in several places; congestion and softening of the brain.

The best and most classical history of the disease is given by Hirsch in his well-known treatise on " Historisch-Geographische Pathologie," to which the reader interested in this phase of the subject is referred. He divides its history into four periods :

1. 1805-1830, during which the disease was general in the United States. In Europe it occurred in isolated epidemics.

2. 1837-1850. During this period there were wide-spread epidemics in France, Italy, Algiers, the United States, and Denmark.

3. 1854-1875. In this period the disease was widely diffused throughout most of Europe, the adjoining countries of Western Asia, the United States, and parts of Africa and South America.

4. 1870-1882. During this period there were isolated epidemic outbreaks. We may add a fifth and sixth period— from 1893 to 1903, and from 1904 to the present time. In these periods there were extensive epidemics in the United States, Portugal, Germany, England, and France.

The following brief historical account is based on the studies of Hirsch and Jacobi.

The First Period (1805-1830).— During the first period the disease was epidemic not only in Medfield but also in New Hampshire, Connecticut, New Jersey, Vermont, Virginia, Kentucky, Ohio, New York, Pennsylvania, and Maine. From 1814 to 1816 epidemics occurred in all the New England States. From 1816 to 1823 no severe epidemics were observed. In 1823 there was an epidemic outbreak in Middletown, Conn. The epidemic in Trumbull, Ohio, in 1828, closed the first period in the United States. Three important contributions to the American literature of the disease were made in this period : the paper by Danielson and Mann, already mentioned; the communication by a committee of the Massachusetts Medical Society (consisting of James Jackson, Thomas Welch, and J. C. Warren) ; and the classical book by Elisha North entitled, " A Treatise on a Malignant Epidemic Commonly Called Spotted Fever." The epidemics were characterized by various eruptions and by the occurrence of pulmonary complications.

In Europe the disease prevailed in Brianca, Danzig, Brest, Paris, and Metz. The frequency of eruptions and respiratory complications was noted here also.

The Second Period ( 1837-1850) .—In the United States the disease was wide-spread from 1842 to 1850. In 1842 Rutherford County, Tennessee, and Montgomery, Alabama, were visited by the epidemic. In 1845 an epidemic occurred in Mt. Vernon, Illinois. It prevailed in Arkansas, Vicksburg, Mississippi, Tennessee, and Missouri in 1846-1847. Montgomery, Alabama, was visited for the second time in 1848. In the same year the disease prevailed in Pennsylvania and Worcester, Mass. The negro quarters of New Orleans were invaded in 1850.

In Europe the most wide-spread epidemic during this period occurred in France. It began in the south of France and spread for the next ten years from the southwest to the northeast. By the movements of the 18th Regiment the disease was carried from the Landes to Rochefort, Versailles, Chartres, Metz, Nancy, Strassburg, Schlestadt, and Colmar. It affected chiefly the military population. The epidemic was transported to Algeria and Italy. From 1839 to 1845 wide-spread epidemics occurred in Italy. Epidemics were also seen in Corfu, Gibraltar, Denmark, and Ireland. In this period the clinical features of the disease were carefully studied and described by the French clinicians (Lespes, Tourdes and Faure-Villars, etc. ) .

The Third Period (1854-1875).— In the United States there was subsidence of the disease from 1850 to 1856. Then new outbreaks occurred during 1856 and 1857 in Salisbury, North Carolina, and the western part of New York State. The disease prevailed in the Army of the Potomac in the winter of 1861-1862. In 1862-1863 it invaded the army camp around Newbern, N. C. It reappeared in Massachusetts in 1864-1865. Philadelphia had an epidemic in 1863-1866. During the same period it was prevalent in Indiana and Iowa, among the Confederate troops at Norfolk, Va., at the military school in Newport, R. I., Mobile, Alabama, Illinois, New Jersey, Vermont, Connecticut, and Ohio. In 1869-1870 meningococcus meningitis was seen in Alabama, Pennsylvania, New Jersey, New York City and Brooklyn, Illinois, South Carolina, and the port of Georgia. Massachusetts, Indiana, and Michigan were visited by epidemics in 1873. In Boston the epidemic occurred in 1874.

From 1854 to 1861 extensive epidemics occurred throughout the whole of the Scandinavian Peninsula, affecting Sweden more severely than Norway. The disease advanced from the south to the northwest, beginning each winter where it had stopped the previous summer. It caused 4158 deaths in seven years. Southern and central Germany was invaded during 1863-1866. Epidemics were also seen at this time in Austria, Hungary, and Russia. The disease was epidemic in Ireland from 1865 to 1868.

The Fourth Period (1876-1882.— In this period no very extensive epidemics are recorded, but the disease prevailed in the form of localized epidemics in France, Italy, Germany, Austria, and Scandinavia. There are no records of epidemics in the United States.

The Fifth Period (1893-1903).— In 1893 an extensive epidemic occurred in New York City, which was described by Berg. In the same year the disease appeared in the Lonaconing Valley in Maryland, and was carefully studied by Flexner and Barker. The epidemic in Massachusetts during 1897-1898 gave rise to the admirable contribution by Councilman, Mallory and Wright.

During this period epidemics were seen in France, Germany, Austria, Norway, Scotland, Ireland, Bosnia, Italy, and Algeria. The severe epidemic in Portugal during 1901-1903 gave rise to a valuable contribution by Bettencourt and Franca. In this period the bacteriology of the disease became established on a firm basis.

The Sixth Period (1904- ).— The disease prevailed in New York during 1904 and 1905. In 1905 there were 2755 cases. There was a severe epidemic in Prussia from 1905 to 1907. The provinces chiefly affected were Silesia and Westphalia. In Great Britain severe epidemics were present in Glasgow, Edinburgh, and Belfast. During 1908-1910 an extensive epidemic was seen in France. During 1910 a severe epidemic occurred along the Pacific Coast. In 1911 the disease spread to the Southwestern States, affecting chiefly Texas and Louisiana.

The extensive researches undertaken during this period have shown the importance of the germ carriers in the spread of the disease. In this period the culmination of the practical study of the disease was reached when the serum treatment was developed.

Bibliography.

Viesseux: Jour. gen. de Med., 1806, xi, 163.

Mathey : Jour. gen. de Med., 1806, xi, 243.

Danielson and Mann : Med. and Agricultural Register, 1806,

i, 65.

North: A Treatise on a Malignant Epidemic Commonly

•called Spotted Fever, New York, 1811. Jackson, Welch, and Warren : Report of Committee to Mass.

Med. Soc, Med. Communications, 1813. Tourdes : Histoire de l'epidemic de Meningite cerebrospinal

observee a Strassbourg en 1840 et 1841, Strassburg, 1842.

Frothingham: Amer. Med. Times, 1864, viii, 207. Niemeyer: Die epidemische Cerebrospinalmeningitis, Berlin,

Webber: Boston Med. and Surg. Jour., 1866, lxxv, 29. Hirsch : Die Meningitis Cerebrospinal epidemica, Berlin,

1866.

Upham : Boston Med. and Surg. Journal, 1867, lxxvi, 485. Stille: Epidemic Meningitis, Phila., 1867. Clymes : Epidemic Cerebrospinal Disease, Phila., 1872. Upham: Boston Med. and Surg. Jour., 1874, xci, 221. Hirsch: Historisch-Geographischc Pathologic, Stuttgart,

1886, 2Aufl.,iii.

Flexner and Barker: Amer. Jour. Med. Sciences, 1894,

cvii, 155.

Berg: Archives Pediatrics, 1894, xi, 352. Jaeger: Die cerebrospinalmeningitis als Heeresseuche,

Bibliothek Coler, Berlin, 1901.

Chapin: Med. News, 1904, lxxxiv, 1063. Jacobi : Transactions Med. Soc. State of New York,

1905, 89.

Netter and Debre: La Meningite Cerebrospinal, Paris,

Chapter II

History. — In 1884 Marchiafava and Celli found at autopsy, in two cases of epidemic meningitis, oval micrococci within the protoplasm of leucocytes and endothelial cells. As no cultures were made, and the result of staining by Gram method is not mentioned, it can only be surmised, but not proved, that these observers were dealing with the meningococcus. Leichtenstern, in 1885, during an epidemic at Cologne, comprising 41 cases, saw, on microscopic examination of 9 cases, intracellular diplococci, cultures of which yielded a number of bacilli, and cocci which, although of the same shape, varied markedly in size. Schwabach, as quoted by Councilman, Mallory and Wright, also found diplococci in the pus-cells of the discharge from the ear in a case of otitis media secondary to meningitis. Previous to this time the only identifiable organism found in the meningeal exudate was the diplococcus pneumonia?. Practically all authors of this period, including Weichselbaum, were of the opinion that the pneumococcus was the only organism capable of producing a primary meningitis.

In 1887, however, Weichselbaum found, in the meningeal exudate and ventricular fluid of 6 out of 8 cases of primary apparently sporadic cases of meningitis, an organism clearly not the pneumococcus and which he named diplococcus intracellularis meningitidis. It was a Gram-negative diplococcus occurring partly within and partly outside the pus-cells. Culturally it was shown to be an obligatory aerobe, whose optimum growth temperature was 37° C. It grew best on media containing animal proteids and required transplantation every day or second day. It possessed feeble pathogenic powers, but direct inoculation in the meninges of dogs produced meningitis and encephalitis. Since in the other two of the eight cases Weichselbaum found the pneumococcus, he expressed the guarded opinion that both of these organisms might produce a primary meningitis. Moreover, as at that time, to his knowledge, there was no epidemic of meningitis in Vienna, he did not feel justified in claiming an important role for this diplococcus in the causation of epidemic meningitis.

Though his painstaking studies were confirmed by Goldschmidt in the same year and by Edler soon thereafter, the discovery aroused but slight interest and was soon almost wholly forgotten.

Isolated finding of the meningococcus was reported now and then. Weichselbaum, however, despite unremitting search, did not meet with this organism again until 1895. By this time the clinical study of meningitis had been immeasurably advanced by Quincke's announcement in 1891 of his method of obtaining cerebrospinal fluid in the living by lumbar puncture.

In 1895 Jaeger, while studying a small epidemic at a garrison in Stuttgart, found in 14 cases at autopsy an organism which he identified with the Weichselbaum diplococcus. It was partly intracellular, being found at times within the nuclei. While Gram-negative in sections, it stained by Gram in the exudates and cultures. It grew well on agar, glycerin agar, and bouillon at temperatures ranging between 22° and 37° C, and showed considerable resistance to external influences. Chains of from twenty to thirty individuals were seen in two cultures. At times a capsule was demonstrable. Despite the obvious morphologic and cultural differences between this organism and the diplococcus described so carefully by Weichselbaum, Jaeger identified the two, and claimed that this diplococcus, and not the pneumococcus, as had been generally accepted up to this time, was the sole infective agent of epidemic cerebrospinal meningitis. His publication, unlike that of Weichselbaum, aroused great interest, and in the sueceeding years many apparent confirmations of his observation were reported.

Heubner, in 1896, found, in the lumbar-puncture fluid of two cases, a diplococcus which presented all the characteristics described by Weichselbaum. In three other cases, however, he demonstrated the presence of a Gram-positive diplococcus which formed chains and grew at room temperature. By injecting this organism in the spinal canal of a goat, he produced acute meningitis.

A period of great confusion followed. Some confirmed Weichselbaum's observations, others those of Jaeger, while still others attempted to identify the meningococcus with the pneumococcus. Soon thereafter the view became quite prevalent that there were two types of the meningococcus, the Weichselbaum type and the Jaeger-Heubner type. Considerable light was thrown on this phase of the meningitis question by the extensive studies of Councilman, Mallory and Wright (111 cases, 55 lumbar punctures, and 35 autopsies), Faber (60 cases), Albrecht and Ghon (30 cases), and Bettencourt and Franca (271 cases). The more recent studies during the large epidemics in Germany, America, England, and France, aided as they were by the development of the fermentation test and the modern serum reactions, have shown conclusively the untenability of the contentions of

Jaeger and his followers, and completely established the constancy of those characteristics of the organism originally described by Weichselbaum. An explanation for the strange results obtained by the Jaeger school was found in the difficulties surrounding the growth of the meningococcus on artificial media and the ease with which other organisms that grow under less exacting conditions contaminate the media employed for its cultivation. In animal experiments the ready invasion of more resistant secondary micro-organisms was another frequent source of error. By his studies of the morphological, cultural, fermentative, and agglutinating properties of the two diplococci, v. Lingelsheim has shown that they can not be considered to belong to the same species. To avoid confusion in the future, he prefers to call the Jaeger coccus, diplococcus crassus.

The following account of the bacteriologic features of the meningococcus is based in part on the admirable paper of Elser and Huntoon.

Staining. — All the ordinary aniline dyes stain the meningococcus with great ease. It is now well established that the meningococcus is invariably Gram-negative, i.e., it takes the counterstain. This staining characteristic of the meningococcus is of great diagnostic importance, as it offers a quick and reliable method of identification of this organism in the cere-

0 ^^r^fc IS?

I i'. I -A, cerebrospinal exudate Diplococeui intraeellularia. H.

4 ,jjj bo o

'3 -3

3 o a; T3

3 O

a, brospinal fluid. The Neisser stain frequently shows the presence of metachromatic granules which are microchemically identical with the Babes-Ernst bodies. The number and size of these granules vary with the strain of the organism, its age, and the culture-medium on which it grows. When grown on glucose ascitic agar at 36° C, the granules begin to appear after six hours, and attain their maximum size within eighteen hours. They disappear completely after a short exposure to room temperature, or after more than a week's growth on an artificial medium.

Morphology ( Fig. 1 ) . — The typical form of the meningococcus is that of two hemi-ellipses apposed by their flat surfaces and separated from each other by a linear space. While the double coccus is the predominant form, tetrads and small groups of diplococci are not infrequent. Isolated single cocci occur more rarely. The meningococcus shows no distinct capsule. At times a mucinous envelope is seen, which has been mistaken by some observers for a capsule. It may also be surrounded by an unstained zone which is due to contraction of the cell envelope or retraction of the culture-medium.

In the exudate obtained by lumbar puncture, the diplococci are often found within the protoplasm of the leucocytes. At times these are completely filled with meningococci. The relative number of intraand extracellular organisms varies with different specimens of cerebrospinal exudate, and seems partly dependent on a difference in the strains of the organism. Following the injection of serum, the organisms, if at all demonstrable, are very frequently confined to the protoplasm of the leucocytes. The phagocytic cells may be normal or degenerated.