Epidemic cerebrospinal meningtis

Preface

My studies in the Research Laboratory of New York and during the Epidemic of Texas in 1912, afforded me a rare opportunity to apply the Laboratory studies of meningitis at the bedside of the patient and to demonstrate the importance of utilizing both laboratory and clinical observations for systematic control of an epidemic and for properly treating the disease.

The studies in Dallas in the municipal control of the epidemic and the coincident studies in the Dallas Meningitis Hospital, enabled me to apply in connected, systematic order many of the excellent observations which had been recorded by different workers. Many of the experiences in the Laboratory and at the bedside so obtained are recorded in these pages. Particular attention has been given to a description of methods employed in scientific municipal control of epidemics, especially with regard to careful, scientific quarantine and the application of specific preventive measures. Many observations on the blood-pressure in meningitis are noted and the method of controlling the administration of the antimeningitis serum by changes in blood-pressure is carefully described. Toward the end of the Texas epidemic, experimental studies on prophylactic vaccination against meningitis were carried out. I hope that this study will stimulate further research which will help to establish this measure as a dependable preventive against the disease.

The purpose of the work throughout is to convey a thorough yet simple description of the clinical and laboratory findings in the disease and to so interpret the laboratory descriptions as to familiarize the reader with their application in treatment and in clinical analysis of the disease.

I take pleasure in expressing my thanks to Dr. William H. Park for his encouragement and assistance to me in my work in the Research Laboratory and to Dr. Simon Flexner for his interest and valuable suggestions during the Texas meningitis epidemic.

ABRAHAM SOPHIAN, M. D.

Kansas City, Mo.

XI

Chapter I. Page

Historical — Predisposing Causes — Bacteriology of the Meningococcus and its Allied Organisms — Portal of Entry of the Meningococcus into the Human Body — Dissemination Disease — Resume of Etiology of Meningitis as to Epidemiology, Bacteriology, Portal of Entry of the Organism, and Mode of Transmission.

Chapter II

Infections Produced by the Meningococcus Preceding Meningitis — Acute General Diseases not due to the Meningococcus, Accompanying an Attack of Epidemic Meningitis — Symptoms in the Acute Form of Meningitis — Chronic Meningitis — Posterior Basic Meningitis — Clinical Differential Diagnosis between Epidemic and other Forms of Meningitis Relapses.

Chapter III

Cerebrospinal Fluid — Other Laboratory Aids in Diagnosis of Epidemic Meningitis — Blood Examination — Presence of Meningococci in Other Secretions.

Chapter IV

General Meningococcus Sepsis — Pressure Complications — Complications of Local Involvement of Central Nervous System — Resume of Symptoms Occurring During Convalescence Course of Epidemic Meningitis.

Chapter V

Blood-Pressure in Epidemic Meningitis — Effect on Blood-Pressure of Withdrawal of Fluid by Lumbar Puncture — Effect of Injecting Serum on the Blood-Pressure — Interpretation of Observation on Blood-Pressure in Meningitis — Observations on Pulse Rate During Lumbar Puncture.

XIII xiv CONTENTS.

Chapter VI. Page

The Anatomy of the Cerebrospinal Meninges, and of Lumbar Puncture — Lumbar Puncture — History of the Introduction of Specific Antimeningitis Serum — Preparation of the Antimeningitis Serum — Standardization of the Antimeningitis Serum — Prophylactic Measures Against Epidemic Meningitis — General Remarks on Curative Treatment — Serum Treatment of First or Premeningitic Stage (accumulative stage) (General Bacteremia) — Classification of Active Treatment — Serum Treatment of Meningitis — Cases with very Thick Plastic Exudate — Serum Treatment of Cases with Dry Canal — When to Discontinue the Further Injection of Serum — Relief of Hydrocephalus in Acute Stage — Acute Meningitis — Treatment of Subacute and Chronic Forms of Meningitis— Treatment of Complications and Sequelae — Analytical Study of the Effect of Serum Treatment of Epidemic Meningitis — Prognosis.

ILLUSTRATIONS.

FIGURE

XXIII. Page

Pure culture of meningococcus 21

Patient actively ill six days with epidemic meningitis .... 72 Boy of eleven, ill forty-eight hours with epidemic meningitis . . 73 Alcoholic patient, ill thirty-six hours with epidemic meningitis . 74 Patient violently ill with acute epidemic meningitis .... 75 Patient ill eight and one-half months with epidemic meningitis . '84

Patient ill six weeks with epidemic meningitis 90

Diagram to show the connection of the subarachnoidal space in

the brain and the cord 162

Scheme to show the relations of the Pacchionian bodies to the

sinuses 163

Diagram of a cross section through the dorsal spine, showing how the arachnoid membrane may be adherent to the posterior surface of the cord 166

Diagram of a cross section through the dorsal spine, showing how the subarachnoid space may completely surround the

cord 167

Diagram of cross section of dissection opposite the fourth lumbar interspace 168

Diagram of cross section of dissection at level of fourth lumbar

interspace 169

Illustrating the operation of lumbar puncture and the technique

in injecting the antimeningitis serum . . . . '. . . . 171 Apparatus for injecting antimeningitis serum ....*.. 210

Needle and trocar for author's apparatus 210

Serum container for author's apparatus 210

Rubber tube for author's apparatus . . . . . . . . . 210

Rubber bulb for author's apparatus 210

Microphotograph illustrating stained sediment of cerebrospinal fluid removed from a case of epidemic meningitis at the beginning of the disease, before serum treatment was instituted 245 Microphotgraph illustrating appearance of sediment 24 hours

after 30 c. c. of serum had been injected subdurally . . . 245 Microphotograph illustrating stained sediment of cerebrospinal fluid obtained 24 hours after the second dose of antimeningitis serum 245

Microphotograph illustrating sediment of the cerebrospinal fluid 48 hours after the third dose of serum 245 xv

Chapter I. Etiology

HISTORICAL. (FROM HIRSCH.)

Hirsch divides the history of epidemic meningitis for epidemiographical purposes into four periods. The first, from 1805 to 1830, shows us the disease in isolated epidemics at various places in Europe, but more general in the United States. In the second period, from 1837 to 1850, meningitis becomes prevalent in widespread epidemics in France, Italy, Algiers, the United States, and Denmark. During the third period, from 1854 to 1875, the malady reaches its widest diffusion throughout most of Europe, the adjoining countries of Nearer Asia, the United States, and some parts of Africa and South America. The fourth period, from 1876 to the present day, is a return to merely casual epidemic outbreaks, or to more or less considerable groups of cases here and there within its former distribution-area.

First Period. — The earliest information on epidemic meningitis dates from 1805, in which year the disease was prevalent in Geneva and the vicinity of the city in the months of February, March, and April, and among all ranks equally. Next came the epidemic outbreak at Grenoble in February, March, and April, 1814, among the soldiers of the garrison, and the concurrent epidemic in the garrison of Paris. In 1815 there was an epidemic at Metz, and one in the spring of the same year at Albenga, Cereale, and two or three more villages in the province of Genoa. In the spring of 1822, many cases of epidemic meningitis occurred at Vesoul, and in the winter of that year the disease was epidemic at Dors ten' in Westphalia.

In the United States, the disease reached a very considerable diffusion in the first of our periods, and was spoken of by those who saw it under the names of "sinking typhus" or "spotted fever." It appeared first in New Hampshire and Massachusetts, later in Connecticut, New Jersey, Vermont, and Maine (1814). The epidemic kept up continuously at one place or another in New England until 1816. Meanwhile it showed itself in Canada in 1807, in Virginia, Kentucky, and Ohio in 1808, in New York State and Pennsylvania the year after, and, according to not altogether trustworthy information, it was prevalent at a later date in the Southern and Western states as well. The year 1816

l formed the close of that time of sickness. With the exception of two rather localized epidemics, one at Middletown, Conn., in 1823, and the other at Trumbull, Ohio, in 1828, the United States was absolutely free from epidemic meningitis from that date down to the year 1842, so far, at least, as* we may infer from the silence of the epidemiographical authorities.

Second Period. — The second period begins with the breaking-out of epidemics of meningitis simultaneously in two localities of the South of France — Bayonne and the department of the Landes on the one hand, and the districts of Foix and Narbonne on the other. From these centers the malady extended over a great part of France within the next ten years. Its first appearance at Bayonne, in 1837, was in epidemic form, and it was again epidemic there in 1840 ; but between these dates the cases were only occasional, and from first to last it was strictly limited to the garrison. Almost at the same time as at Bayonne, it appeared in the Landes, among a number of villages and small towns along the course of the Adour. In these it affected the ordinary residents ; but it was solely the troops of the garrison whom it attacked at Bordeaux and LaRochelle (where it had been seen already in 1837) ; and it was again confined to the garrison when it reappeared at Bordeaux in 1839. Early in 1838 it showed itself at Rochefort, at first in isolated cases in a regiment that had arrived from the Landes ; but at the end of that year it broke out in the Bagnio, both among the convicts and among the civil and military staff of the prison, while occasional cases were seen at the same time among the inhabitants of the town. At the beginning of 1839 the epidemic appeared at Versailles, in the first instance among those very soldiers who had come from the Landes to Rochefort and had been transferred thence in 1838 to Versailles. It quickly attained the dimensions of an epidemic, which was strictly within the limits of the garrison, as were also the occasional cases of the following year and the second epidemic in the year 1848. Although the malady disappeared from Versailles in 1841, many cases of it came to notice in Paris in the summer of 1842.

In the meantime three new centers of the disease had sprung up in the northwest and northeast of France. One of these was almost entirely within the basin of the Loire. The malady occurred first at Laval in the spring of 1840. It continued to be epidemic in the garrison until the end of the following year, but among the townspeople it showed itself only here and there toward the end of its prevalence. After that, in the winter of 1840-41, there were a good many cases at Le Mans and Chateau-Gonthier among soldiers who had been transferred from Laval ; and at the same time the disease became epidemic, or at all events very frequent, at various places in the country around, having occurred among both the soldiers and the townspeople. The second new focus, smaller than that which we have been speaking of, but also in the northwest of France, included the following : the winter epidemics of 1840 and 1841 among the marines in the barracks at Brest, that of the winter of 1840 among the tioops at Caen, and that of the spring of 1841 in the garrison of Cherbourg. The third new center was in the northeast of France. It began with an epidemic of meningitis in the winter of 1839-40 in the garrison of Metz ; in the autumn of 1840 the sickness appeared at Strassburg, where it lasted both among the military and in the town until the summer of the year following, having meanwhile spread, along with detachments of troops, to a number of places near, such as Schlettstadt, Hagenau, Buxweiler, and Wasselonne, at all of which, except Schlettstadt, it was confined to the military. Its next appearance was in 1841 at Nancy, where all the cases but one were among the soldiers; and lastly it showed itself at Colmar, but only in occasional cases in the garrison.

With the year 1842 that succession of epidemics comes to an end. In the years immediately following, it would appear that cases of the disease were seen only now and then in various garrison-towns of France. It is not until 1846-50 that we again meet with references to extensive epidemics of meningitis among the military, including the following : in the garrison of Avignon and Lyons from autumn, 1846, to spring, 1847 ; among soldiers at Nimes, Toulouse, St. Etienne, and Metz in the winter of 1847-48 ; during the same season in Paris, where the disease went on until the spring of 1849 ; also in Orleans, where there were some cases among the townspeople toward the end of the epidemic, and in Bourges ; at Lille in the spring of 1848, and at Toulon in 1850. Among the civil population during this period, the malady became epidemic only twice — in the winter of 1848-49 at Corbeil, and the same winter at Petit-Bourg (Bourbon- Vendee), where it was seen among the pupils of the "colony" and in some other young persons.

The occurrence of epidemic meningitis in Algiers had probably some connection with its general prevalence in France. It appeared in that colony first at the beginning of 1840 in the villages of Setif and Bathna, situated on the plateau of the province of Constantine ; at the same time it occurred at the military post of Douera, not far from Algiers, being also in an elevated situation, where most of the cases were among the French troops. Early in 1841 the disease appeared in the town of Algiers itself, and in the village of Blidah on the slope of the Lesser Atlas to the southwest of Algiers ; it was general among both the military and the civil population, and in the winter following (1841-42) it attained a very wide diffusion through the central and eastern parts of the country (provinces of Algiers and Constantine). In 1844 meningitis was epidemic in the town of Constantine; and in the winter of 1845-46 in Philippeville, Doura, and other towns and villages of each of the above-named provinces, on this occasion principally among the French troops. But the worst epidemic in Algiers was in the winter of 1846-47, when the disease was prevalent not merely in a number of towns of Algiers and Constantine, but also, and for the first time, among the Arab population in remote parts of the country.

Next to France, the widest diffusion of epidemic meningitis on Europeon soil during the second period was in Southern Italy. Our earliest information of it there came from the villages of Mignano and Cervaro (Terra di Lavoro) in the winter of 1839-40. This Italian epidemic closes with the outbreak in the spring of 1845 in the Terra di Lavoro, at the villages of Alife and Piedemonte.

The only other country of Europe in which epidemic meningitis was prevalent to any considerable extent during this period (1845-48) was Denmark. It broke out first in the spring of 1845 in the sanitary district of Frysenborg (province of Aarhus, Jutland), where it showed an epidemic character and received the name of "hjernfeber" (brain fever). Many cases of it were seen at the same time in other parts of Jutland, as well as in Fiinen, Lolland, and Seeland (especially Copenhagen). It reappeared in the winter of 1846, this time mostly in Iceland; and there were similar accounts of it from various parts of the kingdom! in the winters of 1847 and 1848.

In other parts of Europe meningitis occurred during this period in merely isolated epidemics or in small groups of cases. From Spain there was mention of a slight epidemic at Gibraltar in 1844; it was almost entirely among the townspeople, only a few cases having been seen among the troops. In the winter and spring of 1845-46, it was seen in several Irish workhouses, including those of Dublin, Bray, and Belfast ; and occasional cases of it occurred at the same time in Liverpool. In the summer of 1850 it reappeared in Dublin, and continued into the winter, although of a very mild type ; and there were a few cases of it at Rochester the same year. For Germany also, there are references to few slight epidemics of "encephalitis" and "acute hydrocephalus," which in all probability relate to the form of meningitis here in question : one of these was at Meiningen in 1834, others in the spring of 1835 at Barmen, Bergheim, and Mimstermayfeld in the Rhine country, and another in the summer of 1843 at Steinheim in the circle of Hoxter, Westphalia. A number of typical cases of meningitis epidemica were seen at Wurzburg in June, 1851 ; perhaps that was also the nature of the epidemic which was prevalent in the summer of 1853 at some other places in Lower Franconia (Uffenheim, Ochsenfurt Aub), although Hirsch is unable to speak positively about it.

During the second period, epidemic meningitis again became very prevalent in the United States, having been epidemic from 1842 until the winter of 1849-50. The malady was seen first at the beginning of 1842 in the county of Rutherford in the heart of Tennessee, and at Montgomery, Alabama. We hear nothing of it in 1843 and 1844; but in the autumn of 1845 it appeared at Mount Vernon, the chief town in Jefferson County, 111., and at other places in the south of that State ; in the winter of 1846-47 in the counties of Bentonville and Union, Arkansas ; at the beginning of 1847 in Vicksburg, Miss. ; and the same year in Hardman County, Western Tennessee, at Rocheport in Boone County, Mo., and at New Orleans among a regiment of recruits who had come from Mississippi. In the spring of 1848 it reappeared in Montgomery, and extended to the plantations in the neighborhood; the same season it was very destructive in the extreme west of Pennsylvania, in Beaver County on the Ohio. In March, 1848, it was seen in the towns of Millbury and Sutton, in Worcester County, Mass., and there were a good many cases among negroes at New Orleans in January and February of 1850.

Third Period. — This begins with the outbreak of the disease in 1854 in Sweden, a country hitherto quite free from' it but now destined to most serious visitation lasting more than ten years. Early in 1854, epidemic menigitis was seen at Gottenburg, and toward the end of that year in Blekingelan and Kalmarlan, but only in somewhat scattered cases. It was not until the first six months of the year following (1855) that it attained to epidemic prevalence in these centers; and durjng the same season smaller foci of it were established here and there in the provinces of Christianstad, Jonkoping, Bohus, and Sodermanland. In its -progress northward from the southern extremity of the country it went no farther than the town of Kalmar by the end of the season. During the last six months of 1855 the epidemic was extinct; but it broke out anew in January, 1856, and now spread northward from its former seats through the northern part of Kalmarlan and the provinces of Jonkoping and Oestergottland ; meanwhile small epidemics appeared here and there in Blenkinge, Bohus, Gottenburg, Elfsborg, Oerebro, and Wermland. That year its northern limit was Philipstad in Wermlandlan. In May the epidemic had died out everywhere, to reappear at the beginning of the following year. Its distribution-area was now a wide zone including the eastern shore of Lake Wenerand, the northern parts of Skaraborglan, the country north of Lake Wetter as far as the southern part of Oerebrola, both shores of Lake Malar with the northern division of Sodermanland, the southern part of Westmanland, and the districts of Upsala and Stockholm. That season the epidemic died out in June, having extended as far as the latitude of 61° N. It was in the year 1858 that epidemic meningitis reached its greatest height in Sweden. It was most severe in the provinces of Upsala, Westmanland, Oerebro, Wermland, Stora- Kopparborg, and Gefleborg. It reached that year to the latitude of 63° N., which has been its northernmost limit in Sweden.

In the following season (1859) a considerable decline of the epidemic was remarked, both in the number of its several foci and in the number of cases in each. The only considerable epidemics were in Stora-Kopparborg and Gefleborg; in the districts of Upsala and Skaraborg there were smaller epidemics, as well as a certain number of cases in the southern provinces. In I860 the disease was confined within still narrower limits, being of more considerable extent only in Oerebrolan at the northern extremity of Lake Wetter. From 1861 to 1864 there were merely occasional cases at a large number of places. In 1865-67 slight epidemics sprang up once more in the provinces of Upsala, Halland, Malmohus, Stora-Kopparborg, Elfsborg, Kalmar, Jonkoping, Oerebro, Sodermanland, Oestergottland, and Gottland. Since that time no epidemics of meningitis have been seen in Sweden. The number of deaths from the disease officially returned in 1854-60, and 1865-67 was 4577.

Norway has remained almost exempt. Only twice has the epidemic been in that country : viz., a very malignant form of it during the first three months of 1859 in the village of Opdal (Hedemarken) ; and the year after, to a slight extent, in the village of Rangsaker in the same province. In Denmark, too, there was only one epidemic during this period in a few villages of northern Jutland during the winter and spring of 1875.

Another of the principal seats of meningitis epidemica during its third period was Germany, where it reached its height in 1864 and 1865. The disease had been already seen in 1863 in a few localities of Silesia (Liegnitz and particularly in the valley of the Neisse) ; but in the winter and spring of 1863-64 it broke out almost simultaneously at a number of points in East and West Prussia, Posen, Brandenburg, and Pommerania. and was epidemic therein until the end of the following winter. The same season witnessed its first outbreak at Leipzig and at a number of places in Thuringia.

In South Germany its chief seats were the Bavarian departments of Central, Lower, and Upper Franconia.

By the end of 1866 the disease in Germany had lost its epidemic character ; and in after years it was seen only in sporadic cases, unless in a few limited epidemics : such as those of Danzig and Konigsberg in the winter of 1869-70, and those of Berlin, Bonn, Mannheim, and Munich, in the winter and spring following.

In Austria and Hungary epidemic meningitis had a very limited diffusion, so far as we can gather from the scanty records of it furnished by these countries. In the spring of 1863 it was prevalent in the orphanage of Vienna ; in the winter of 1865-66 in the Hungarian county of Gomor; and in the winters of 1866-67 and 1867-68 at Pola and other places in Istria, and at Trieste and some adjoining villages (St. Vito, Servola, St. Giacomo) . In Russia it was first seen in the spring of 1863 in the government of Kaluge ; and next year in the Caucasus ; it was also in the summer of 1864 that the first cases appeared at St. Petersburg, where the disease lasted until the summer of 1868 without becoming epidemic to any considerable extent. To the same period belongs its earliest epidemic outbreak in Russian Poland; the first cases were seen at Kolo in 1865 ; it came to Warsaw in January and February, 1866, and about the same time it was in the neighborhood of Konin, Paryszew, and Minsk (Lithuania). From 1867 to 1869 it became more general in these provinces, and broke out also at a number of points in Galizia. Early in 1866 there had been many cases of it in Moscow ; and in the winter of 1867-68 an epidemic of meningitis developed in Simferopol which spread over the whole of the Crimea and was especially severe in the towns of Bakchi-Serai, Alushta, Sebastopol, and Eupatoria. From Roumania we have an account of a slight epidemic at Jassy in the winter of 1869 ; the same year the disease appeared in Turkey and at Magnesia near Smyrna ; and the year after in Smyrna itself. In Greece it was first seen in 1863-64 in the epharchy of Phthiotis, during the winter of 1868-69 in Nauplia and Milos, shortly in Argos, Tripolis, Athens, and other places, spreading so widely in that and the two following winters that no province of the country except the Ionian Islands escaped.

The south and west of Europe were but slightly affected during this period. In the winter of 1866-67, epidemic meningitis occurred a second time in Dublin and other parts of Ireland, particularly among the soldiers; and on English soil in a village near Lincoln the same season. In the Netherlands it was seen in the winter of 1860-61 in the garrison of Arnheim ; and in the spring of 1867 a slight epidemic sprang up in the village of Giethorn (Overyssel). In Switzerland occasional cases were seen at Basel in 1859, and again in 1870; but in 1871 it was more extensively epidemic there and in a number of Bernese villages. In France there were some cases among the Bordeaux garrison during the winter of 1867-68, and a small epidemic among the troops in Strassburg in the spring of 1868. In Italy it was seen at Bologna for the first time in 1873, and at Rome in the winter of 1873-74. In the spring of 1874 it spread for the second time widely over Southern Italy, especially in the vicinity of Naples and around Spinazzola, Minervino, Castelana, and other places in the province of Terra di Bari, in the district of Salerno, and in the provinces of Foggia, Capitanata, Apulia, and Campania, where it continued to be prevalent until the winter of 1875-76; it was epidemic also around Cremona in the summer of 1875. From, Portugal we hear of it in the winter of 1861-62 on the hilly ground along the right bank of the Tagus near the Spanish frontier, especially among the villages of M on forte, whence it extended in the directions of Oporto and Lisbon.

In Asia, besides the outbreak of the disease already mentioned near Smyrna, it was reported at Jerusalem in the spring of 1872, the cases having been merely occasional, and in Persia in 1874 and 1875. In Africa there was a slight epidemic in January, 1868, at Setif in Algiers in a company of Algerian tirailleurs.

The United States was again the chief seat of epidemic meningitis in this its third period. From 1857 to 1875 scarcely a year passed without its being seen over a larger or smaller area, its diffusion from first to last covering the whole of the country.

This series of epidemics begins with outbreak of the malady in 1856-57 in two regions far apart, one of them being North Carolina, whence we have details of it in Salisbury (Rowan county), and the other New York State, where its visitation was mostly in the western and central counties of Onondago, Chemung, and Madison. During the Secession War of 1861-63 the sickness became more widely spread. In the winter of 1861-62 it appeared in the army of the Potomac encamped near Washington; at the same time in Livingston county, Mo., among both soldiers and civilians ; in that and the following winter among negroes sent by the Confederates to Memphis ; and in the winter of 1862-63 among the troops encamped in and around Newbern, Craven county, N. Carolina. In the winter of 1863 a severe epidemic arose at Philadelphia and other places in Pennsylvania ; in that and the following year it spread over a large part of the State, and was still going on in Philadelphia as late as the winter of 1865-66. In the winter of 1862-63, simultaneously with the outbreak in Pennsylvania, it appeared in LaGrange and other places in the north and south of Indiana, in Norfolk, Va., among the Confederate troops, in Iowa, at Newport, R. I., in the military school, making its first visit, and at Mobile. In the winter of 1863-64 it was epidemic in the southern and central parts of Illinois, in a few localities of New Jersey, in Vermont and along the Connecticut river, in Springfield county and some parishes of Licking county, Ohio, at Washington in two hospitals and an orphanage (having been imported from the seat of war), at Mobile and in Green county, Alabama, and in the spring of 1864 in Frederick county, Maryland.

In 1865 the sickness would appear to have been in abeyance, if we may judge from the absence of all reference to it. But in the winter of that year it broke out anew in various parts of Illinois; in the spring of 1866 in Breckenridge county, Kentucky, and once more in Mobile; and in the winter of 1866-67 at Philadelphia. For the winter and spring of 1867-68 we have accounts of the prevalence of epidemic meningitis in Huntingdon county, Pa. ; in New York, where it was confined to one block of houses ; and in Findiey, Ohio. In 1869 we hear of it in various places in Indiana. In the winter of 1869-70 it reappeared in Green county, Alabama, and at Albion, in Erie county, Pa. : in the summer of that year it occurred in several parts of Virginia ; and toward the end of the year in the south of Mississippi State. In 1871 it became widely diffused in Minnesota and in Pennsylvania ; and in the latter it continued prevalent for two years longer in a number of places, such as Philadelphia and counties of Lancaster, Huntingdon, Lehigh, and Schuylkill. Coincident with this general prevalence in Pennsylvania was the outbreak of epidemic meningitis in 1872 in New Jersey, in New York City, and Brooklyn, and in some other parts of the State, such as Westchester and Onondaga counties ; also in Montreal, Canada ; in Edwardsville, Crawford, and places in Illinois ; and in a number of localities of South Carolina. In 1873 Massachusetts had a severe visitation, after an immunity of many years. The same year the malady was prevalent in the vicinity of Lake, Indiana ; toward the end of the year an epidemic sprang up in Michigan, which overran several counties and was particularly severe in Monroe county. Subsequent to 1874 the United States authorities are silent about epidemic meningitis; so that the disease as a widespread malady would appear to have ended for the present on American soil with the extinction of the epidemic last mentioned. Therewith also' ends the third in the history of the sickness.