318 CALIFORNIA STATE JOURNAL OF MEDICINE Vol. X, No. 8 i ORIOI64AL ARTIGLeS RABIES, AND ITS PRESENT STATUS IN CALIFORNIA.* `By WILBUR A. SAWYER, 116. D., Director of the Bu- reau of the Hygienic Laboratory of the California State Board of Health, Berkeley. Efforts to check the spread of rabies, or hydro- phobia, among the dogs of California are greatly hampered by the difficulty in obtaining authorita- tive statements of fact regarding the present situa- tion. Many controversial articles and conflicting theories are being read and discussed, and it is no wonder that the public and, to a large extent, the medical profession of California are unaware of the true state of affairs. This article will attempt to present the facts needed by those who are try- ing to check the spread of the disease among dogs and to make its transmission to people impossible. The early part of the present epizoijtic was reported by Black and Powers l in November, 1910, and the history of the disease up to April I, 191 I, was presented with the available statistics in an article published by myself * in July of that year. Since then the involved territory has been greatly enlarged and the most populous part of the state has been `invaded. The center of maximum involvement has passed from Los Angeles to Fresno County and finally to San Francisco. Figure I is a series of maps which shows at a glance how rapidly the disease has spread. The change in the shaded areas shows the increase in the number of counties involved, and the stippled counties represent an area invaded while the sta- tistics here presented were being gathered to- gether. It must be kept in mind that these maps, except some of the circles representing human deaths, are based on the results of laboratory ex- aminations and not merely. upon the interpreta- tion of symptoms. RESULTS OF LABORATORY EXAMINATIONS. At the Hygienic Laboratory of the State Board of Health, in the year beginning April I, rgr I, and ending March 31, 1912, the heads or brains of 122 animals were received for examination. Five of the heads were in an advanced stage of decom- position and could not be examined. Sixteen gave negative results. Of the remaining IOI giving positive findings, 87 showed Negri bodies in the hippocampus or in `other parts of the brain, and 14 others caused typical symptoms of rabies after inoculation into rabbits or guinea-pigs. The IOI positive cases were distributed among the dif- ferent animals as follows: 2 men, 94 dogs, 2 cows, I horse, I cat and I ground-squirrel. Sixty-four people and seventy-eight dogs were reported as having been bitten by the animals which showed evidence ,of rabies on examination. As an in- dication of the increasing prevalence of the disease it will not be out of place to mention that in the two months following the period for which the statistics have just been given 55 examinations were made with positive results in 46 cases. The rapid increase of rabies is shown by the fact that IOI positive cases were examined in twelve months be- * Read before the Sacramento Society for Medical Improvement, June 18, 1912. fore April I, 1912, and nearly half as many, 46, in the two following that date. The specimens giving positive results during the year ending March 31, 1912, are divided between the counties as follows: Fresno, 2g ; Kings, 18 ; Tulare, 16; San Francisco, 12; Kern, 7 ; Merced, 4; San Bernardino, 3 ; Stanislaus, 3 ; Riverside. 2; Madera, 2 ; San Joaquin, 2 ; Imperial, I ; Contra Costa, I ; San Mateo, I. The number of positive examinations increased rapidly during the winter, which is our cool and wet season. This is sufficient answer to the very general superstition that the disease is caused by hot weather and to the claim frequently made that inability to get water is the cause of hydrophobia in dogs: By months the positive examinations are grouped as follows: in 191 I, April, 3 ; May, 3 ; June, 4; July, 3; August, 5 ; September, 7; Oc- tober, IO; November, 9; December, 9; in 1912, January, 15 ; February, 18 ; March, I 5. Many examinations for rabies have been made in municipal and private laboratories in Califor- nia. Through the kindness of those in charge the results of these examinations have been obtained for publication and have been combined with the statistics of the State Hygienic Laboratory in the table below. TABLE 1. Results of Laboratory Examinations for Rabies, April 1, 1911, to March 31, 1912. St;;;atoFvgienic Lab- . . . . . . . . . . . . 122 Health Inept. of San Francisco . . . . . _. . . 70 Health Deot. of Los Angeles -. . . . . . . . . . Health Dept. of Long Beach . . Letterman General Hosp., San Fran- cisco . . . . . . . . . . . . . . Dr. W. Ophiils, San Francisco . . . . . . . . . DrA,ty. Tinsser, Palo . . . . . . . . . . . . . Dr. S. P. Black, Los Angeles . . . . . . . . . . . Dr. R. A. Archibald, Oakland . . . . . . . . . . San Fran&co Vet- erinary College. . . I a9 18 2 1 11 8 5 5 3 1 18 18 21 8 .43 46 424 255 Subtracted because examined in more than one labora- tory . . . . . . . . . . . . . . . 5 5 Corrected Total.. . .z % 87 14 47 2 18 0 1 0 8 5 5 5 1 1 18 0 8 1 46 0 23!, G 5 5 z ii 64 48 29 1 0 4 0 29 0 5 To 0 180 POSITIVE CASES BY COUNTIES. San Francisco ................... I 19 Los Angeles ..................... 30 Frcno ......................... 30 Kinrrs .......................... 18 Tulare ......................... 16 San Bernardino .................. 8 Kern .......................... 7 Orawe ......................... 4 Mercrd ....... ;. ............... 4 AUG., rgrz CALIFORNIA- STATE JOURNAL OF MEDICINE Stanislaus . . . . . . . . . . . . . ; . . . . . . . . . 3 Ventura . . . . . . . . . . . . . . . . . . . . . . . . 2 Riverside . ../................... 2 Madera . . . . . . . . . . . . . . . . . . . . . . . . 2 San Joaquin . . . . . . . . . . . . . . . . . . . . . 2 Imperial . . . . . . . . . . . . . . . . . . . . . . . . I Contra Costa . . . . . . . . . . . . . . . . . . . . I San Mateo . . . . . . . . , , . . . . . . . . . . . I 250 POSITIVE CASES BY ANIMALS. Man . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Dogs * . . . . . . . . . . . . . . . . . . . . . . . ...240 Cats . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 cows . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Horse . . . . . . . . . . . . . . . . . . . . . . . . . . I Squirrel . . . . . . . . . . . . . . . . . . . . . . . . I 250 Those who claim that the disease will soon die out if unopposed will find food for thought in comparing the 250 cases of proved rabies of the year beginning April I, rqxx, with the 164 similar cases collected in my report of a year ago * for the seventeen months preceding. This gives a total of 414 positive cases examined in laboratories during the present epizoiitic. DIAGNOSIS BASH) ON SYMPTOMS ONLY. There can be little doubt that the laboratory examinations represent but a small fraction of the total number of cases of rabies in the state. Un- less persons or valuable animals have been bitten or unless the disease is new in a region, many ani- mals die or are killed and buried without its being considered sufficiently important to warrant the trouble and expense of removing the heads, boxing and icing them, and shipping them by express to the laboratory. Diagnoses based on clinical symp- toms are not apt to be reported to the State Veterinarian or the local health authorities unless the suspected animals have come under the ob- servation of a veterinarian or physician who real- ized that the officials should be notified. Replies to a circular letter to the health officers of the southern two-thirds of the state did not show any territory to be involved except the counties al- ready shown to be infected according to the labor- atory records. The cases reported as being diag- nosed as rabies from clinical symptoms alone are probably duplicated in the record kindly furnished by Dr. Keane, State Veterinarian. To his office between April I, 1911, and March 31, 19x2, 285 cases of rabies were reported. Of these, 120 were based on laboratory evidence and are probably in- cluded in the statistics already given. The re- maining 165 are additional cases reported by veter- inarians on the basis of clinical symptoms. These 165 cases came from territory shown on the maps in Figure I to be infected. They are divided among the various animals as follows: dogs 142, cows 12, hogs 6, horses 3, goat I, mule I. RABIES IN MAN IN CALIFORNIA. The mortality among human beings seems very small when comparison is made with the death rate among dogs, which are the chief sufferers. Previ- ous to April I, IgIl, five human deaths had been reported.2 These are briefly reviewed below. The first of these preceded the summer of agog, when the disease began to be prevalent.. I. A man, H. M. S., died with the symptoms of rabies in Pasadena on March IO, 1899, five weeks after being bitten in the face by his dog. Inoculation with brain tissue of the patient pro- duced rabies in rabbits.s 2. M. E. C., a man, aged 30, died with the symptoms of rabies, in Holtville, Imperial County, on Dec. 12, 1909. He had been bitten by a cat. 3. J. S., a boy of IO years, died with symp- toms of rabies on February 21, 19x0, in Los Angeles.4 He had been bitten in the leg by a stray dog. Negri bodies were found in his brain. 4. J. B., a man of 62, died of rabies at Rivera, Los Angeles County, as a result of being bitten in the face by his own dog. 5. E. L., a girl of six years, died of rabies on Dec. 2, rgro, in Los Angeles, seventeen days after being bitten in the lip and nose by a stray dog. Intensive Pasteur treatment was begun, but the unusually short incubation period did not permit its completion and therefore it did not have time to produce the immunity needed for protection. Negri bodies were demonstrated in the head of the dog and later in the brain of the girl. Inoculation with brain tissue of the girl produced rabies in a rabbit.6 This case was described in greater detail in my previous article on rabies in California.? During the year for which the laboratory sta- tistics are being given, April I, IgI I, to March 3 I, 1912, there have been six human deaths from rabies, bringing the total of reported cases up to eleven. That there were not more fatalities can only be accounted for by the large number of per- sons who availed themselves of the Pasteur treat- ment for the prevention of rabies. The remaining six cases are given below. 6. A girl of three years, M. L. C., developed the symptoms of hydrophobia (rabies) and died on June 27, rgr I, near Tulare, Tulare County. The typical symptoms, including the spasms of the throat on attempting to swallow, were present and left no doubt as to the diagnosis. The source of the infection was not ascertained although careful inquiry was made by the attending physician, Dr. John B. Rosson, to whom we are indebted for our information. 7. A boy, aged 15, C. V. B., died of hydro- phobia on August 27, 1911, in Los Angeles. From the report' of this case published by Dr. W. V. Chalmers Francis, attending physician, and from information kindly furnished by him through correspondence, the following facts have been briefly gathered together: About nine months before the boy's death his pet dog, as well as several other dogs in the neigh- borhood, had been bitten by a strange dog. One or two of the animals which had been bitten were later killed on the suspicion of having rabies. The boy's dog developed an acute illness, supposed at the time to be poisoning, and died five to seven 320 CAmXMrA^ STATE 'JoumA~ 0~ MEDICINE Vol. X, No. 8 days after the first symptoms. Among the symp- toms of -the dog were rapid breathing, salivation and weakness of' the hind iegs. The boy took entire care of the sick .animal. Whether the boy was actually bitten' is not clearly remembered, but one of the boys in the family was bitten by the dog at about this time, and the boy who died had open wounds on his hands when he was caring for the animal. The boy was a strong healthy youth who attended school during. the day and acted as life-saver and swimming expert at one of the public baths in' the .evening. On August 22, he began to feel feverish. The next day he took to his bed and complained of stiffness in his legs. He had no appetite. The fol- lowing night he was unable to sleep. On the third day, August 24, he disliked to drink on account of trouble with his throat. He dressed himself and walked stiffly. The following day he became much excited and easily angered. His flushed face wore an expression of fear and anxiety. He com- plained of slight pains in throat, chest, and abdo- men and of difficulty in swallowing. He could not sleep. He answered questions rather clearly, but contradicted himself frequently. Occasionally he had outbursts of passion followed by expressions of regret and apology. He had fear that he would be forced to drink and he exclaimed that he would not drink because it choked him. Drafts of air precipitated spasms of the face so painful that when the door was opened, the patient screamed in terror. Other prominent symptoms were loss of power in the legs, loss of the patellar reflex, irregular breathing, irregular and rapid heart action and ele- vation of temperature to 102' F. Sometimes the patient would not breathe during a period as long as forty seconds. During the remaining two days of life the patient had frequent convulsions and fits of anger. There were noisy delirium, delusions, hallucinations, and unreasoning fear. At times he became rational and complained of burn- ing in his throat, but he would refuse angrily to try to drink. Toward the end he developed em- physema of his face, neck and chest. He died on the 27th of August, the sixth day of his illness. An examination of his brain performed by Dr. Stanley P. Black, -revealed the presence of Negri bodies, and confirmed the diagnosis based on symp- toms. 8. A man of 30 years, W. L. L., died of rabies on .September I, rgr I, in Los Angeles. We are indebted to his attending physician, Dr. H. A. Johnston of Anaheim, and to Dr. Anders Peter- son of the Los Angeles County Hospital for the following information: On June 15, 1911, the man was bitten on the hand by his own pet dog. There were about four small deep wounds. These were cauterized with nitric acid. A veterinarian who examined the dog stated that he suspected rabies and advised observation of the animal. The owner killed the dog against this advice, thus de- stroying further evidence, and refused to take anti- rabic treatment. On August 30, rgrr, 59 days after he was bitten, the man began to feel sick and tired and to yawn frequently. The following night severe symptoms began. He was taken to the Los Angeles County Hospital on August 31. When he arrived, he was semi-conscious and the spasms in his throat were so severe that he could not swallow or speak. He died on September I, the third day of his illness. g. A boy six years old, C. W. B., died of hydrophobia on February 15, 1912, in Santa Maria, Santa Barbara County. Dr. R. W. Brown of that city is to be thanked for furnishing us the important facts in the case. On January 12, 1912, this little boy was play- ing in the road in the country near Santa Maria when a small black dog attacked him and bit him in the face and on the hand. The dog then went on its way and was not seen again. Four hours later the wounds were cauterized. On Feb- ruary rqth, one month after the biting, the boy was visited by Dr. Brown, who found his patient on the bed with an expression of extreme terror on his face. For four or five days the child had not been himself, being at first peevish and dis- inclined to play and later having spells of choking and of "seeing things" on the wall. During the doctor's visit the boy complained of thirst and asked for water, but, when given as little as a teaspoonful, he fell backward suffering agony from the spasm in his throat, and swallowing was im- possible. Early the following morning the little fellow died. IO A man of 21 years, F. A., died of hydro- phobia on March g, 1912, in San Francisco. Through the courtesy of Dr. F. R. Dray, attend- ing physician, the following facts have been learned regarding this case. The young man was the owner of four dogs. One of these was bitten by a dog supposed to be "mad." The dog which was bitten developed rabies and bit one or more of the other three before it died. All four of the animals finally succumbed to the disease. While attempting to give the last of his dogs castor oil, the owner was bitten in the right thumb near the nail. This occurred on February 3, 1912, before the outbreak of rabies in San Francisco had re- ceived sufficient publicity to be generally recog- nized. The young man contented himself with cauterizing the wound with phenol two days after it had been inflicted. On March 2, four weeks after the bite, he be- gan to have pain in the right arm. Two days later he became very nervous and troubled and consulted .a physician. He was unable to swallow some pills intended to quiet him. On the same day he was sent to the German Hospital. On admission he was unable to swallow liquids except with greatest difficulty. During the following night he was rational, but after that he had fre- quent periods of intense excitement, delirium, and convulsive twitching. He had hallucinations lead- ing him to believe that there were various animals in his bed, and his face bore a peculiar drawn ex- pression resembling a smile. Noises or contact precipitated attacks of twitching and rigidity of his muscles. There were no true convulsions. There n-as moderate fever. As he was unable to swallow, AUG., rgrz -. CALIFORNIA `STATE JOURNAL OF MEDICINE 321 nourishment was maintained by rectal feeding. I was invited to visit the patient on March 8th. The disease was far advanced and death was evidently not far away. The patient's face wore .a markedly drawn and worried, or frightened. ex- pression and his open mouth was `filled with foamy saliva. There was moderate cyanosis and the breathing was heavy. He was unable to articulate. The extremities were very weak and somewhat rigid. The patient:died early on the morning of March gth, eight days after he began to feel pain in his shoulder and six days after symptoms of nervousness began. A post-mortem was performed and parts of the brain were sent to -several laboratories for diag- nosis. The results were uniformly positive. for rabies. At the State Hygienic Laboratory, Negri bodies were..demonstrated in the hippocampus. A rabbit and.a guinea-pig were inoculated and both developed rabies. The guinea-pig showed symp: toms of furious rabies for five days. II. A, man of 63 years; J. M., died of rabies on March 21, IgI2, in San Francisco. On Feb ruary 25th this man was bitten deeply in the left wrist and more superficially in the left foot by a dog on the streets of San Francisco. The wounds were cauterized half an hour afterward. The brain of the dog inflicting the wounds was examined at the laboratory of the San Francisco Health Depart- ment and was found to contain Negri bodies. Af- ter a delay of five days the patient came to the Laboratory of the Health Department on March I, and was put under the Pasteur treatment with virus distributed through the State Hygienic Lab- oratory. On the 17th day of treatment, four days before the treatment would have been finished, the patient complained of pain in his arms and chest but especially in his left shoulder. The location of the pain was probably due to the fact that the more serious wounds had been inflicted in the left wrist. He also complained of. a gen- eral aching. The next day he took to his bed. His chief symptoms were loss of appetite, insomnia, nervousness, and pain in his left shoulder and chest. He had a mild fever reaching a maximum temperature of 99.2' F. The next day I had the privilege of seeing the patient. The symptoms were much & already described. The patient's mind was clear and he did not seem specially apprehensive. On tb e evening of the following day, March 29, more characteristic symptoms de- veloped. There was difficulty in swallowing. The next morning he had convulsions and spasms. Chloroform was given for relief. The patient finally became comatose and died at noon, March 21, 1912. A portion of the brain was. examined at the State Hygienic Laboratory and Negri bodies were found in the hippocampus. Animal inoculations were impossible as the specimen had been sterilized by embalming. We are indebted to Dr. W. H. Kellogg of the San Francisco Health Department and Dr. Paul Castelhun, attending physician, for `information re- garding this case. This is the second case in California where the Pasteur treatment was begun but was unable to save the patient because the incubation period was much shorter than usual and not sufficient for the development of immunity. COURSE OF THE DISEASE IN MAN. The chief symptoms of rabies in human beings have most of them been depicted in the cases al- ready .described. In the majority of the people bitten by rabid animals the disease does not de- velop even without treatment, but all of the cases which advance to the point of showing symptoms are fatal in spite of any treatment' as yet known. By taking an average of a large number of cases it has been found that abo'ut 15 per cent of un- treated people, who `have been bitten by rabid ani- mals, develop the disease, while all but 1.3 per cent * could have been saved by treatment. These figures are based only on cases of persons receiving significant bites from animals conclusively shown to be rabid. The mortality is highest from bites which are most severe and those inflicted nearest the central nervous system or large nerve trunks and from virus of special virulence for man, as, fur example, the virus received from wolf bites. The wound inflicted by a rabid animal heals or fails to heal without being noticeably affected by the presence or absence of the virus. After an in- cubation period varying* in man from 14 days to a year, or even longer, but in the great majorit! of cases lying betwen thirty and seventy days, symptoms make their appearance. There may be redness, pain, numbness, or itching at the wound or near it. Nervousness, irritability, and inability to sleep may be the only symptoms for a day or two. A moderate elevation of temperature is a fairly constant symptom. These earliest symptoms are usually followed within a day or two by marked nervous excitability and sensitiveness to ex- ternal stimuli. A draft of air, a touch, or a noise may cause painful local spasms of the facial or other muscles, or general muscular spasms. Moderate difficulty in swallowing is followed, as the symptoms develop, by excruciating pain due to spasms of the throat brought on in greatest severity by any attempt to drink. The dread of these spasms will sometimes lead patients to scream at the sight of a glass of water or at the suggestion of drinking. These symptoms were early inter- preted as fear of water and the disease was named hydrophobia. There are hallucinations and there may be violent fits of anger and even furious mania, but intervals usually occur in which the mind is clear. The breathing becomes irregular and the heart action is rapid. Finally paralysis becomes the predominant symptom and convulsive seizures, con- trollable only by general anesthetics, cease, and death ends the suffering. The course of the dis- ease is usually between three and eight days from the first symptoms. The duration of the disease is shorter in the more severe form, known as the dumb or paralytic type, where the stage of excite- ment is not very marked, than in the furious type of the disease. 322 CALIFORNIA STATE JOURNAL OF MEDICINE Vol. x, No. s COURSE OF THE DISEASE `IN THE DOG. In dogs, as in man, the incubation period is long, varying from 8 days to one year, but seldom exceeding six months and usually lying between 15 and 60 days. As in man, about 15 per cent of the dogs bitten by rabid animals develop the disease. The symptoms in the dog resemble those of man in being chiefly the effects of greatly increased sus- ceptibility of the nervous system to external stimuli. The first symptoms noticed are apt to be a change in behavior. The animal may be more affectionate than usual, but he is more apt to be morose and agitated. He tends to snap and bite, probably be- cause of hallucinations. The voice is frequently changed. Soon difficulty in swallowing appears and paralysis of the jaws and hind legs is apparent. Dogs fairly well advanced in the disease will frequently try to drink and they succeed in wet- ting their dry noses and tongues, but are usually entirely unable to swallow. The water runs back out of their open mouths. The paralysis gradually spreads to the whole body and the animal dies in a few days after the first symptom, usually in 4 or 5 days, possibly in z to IO davs. The symp- toms of rabies vary greatly, and frequently some characteristic symptoms, such as the hanging of the jaw, may be absent. The cases of rabies in dogs are arbitrarily divided into two merging types, furious and dumb rabies. This classification only serves to indicate whether the nervous symptoms show themselves chiefly in excitement and activity or in helpless Fig. 2. Dogs showing symptoms of rabies. The jaw is allowed to hang down and can be closed with difficulty, if at all. Figure 2 shows pictures of three dogs suffering from rabies. They all show the dropping of the jaw, and some of the pictures suggest the muscular weak- ness, especially of' the hind legs. The swollen dry tongue, the bleary eyes, and the emaciation cannot very well be made out in the pictures. The first in the series of four pictures shows a dog which came down with rabies at the Presidio of San Francisco, and I am indebted to Dr. John R. Barber for the opportunity of securing the photo- graph. The other three pictures were taken in Riverside and were kindly furnished by Dr. Geo. H. Tucker, Health Officer of Riverside County. paralysis. The dumb farm is a; a rule the more severe and more rapidly fatal. In the furious type the dog is apt to Icnvr home and to travel long distances. running along aimlessly and attacking without warning animals or persons who may happen to be in his path. Such rabid animals usually look dirty and tired. and the beginning muscular weakness may she\\ itself in a wavering gait. The dog may travel for many miles and for a couple of days before mea!<- ness brings it to the ground to die. Attempts to treat such dogs have resulted frequently in their biting the persons attempting to relieve their suffering. As an example of the distances which rabid dogs AUG., rgrz CALIFORNIA STATE JOURNAL OF MEDICINE 323 sometimes run, introducing their disease into new territory, the following case is of interest. A bull terrier left his home in San Francisco at IO a. m. on April 21, 19x2. No abnormality was noticed by his owners. The next day he killed and tore a dog and attacked a woman in Half Moon Bay, twenty-five miles or more from his home. The dog was shot and the head was sent to the State Hygienic Laboratory, where Negri bodies were demonstrated in the brain tissue. CHARACTERISTICS OF THE DISEASE. Rabies, or hydrophobia, is a specific infectious disease to which all warm blooded animals are susceptible. The disease can only be contracted through the introduction of virus from a previous case of rabies into a wound which enters or pen- etrates the skin and thus permits the infectious agent to come in contact with nerve filaments. The infectious agent, differing in this respect from other known causes of disease, spreads slowly up the nerves to the central nervous system, where it develops and produces characteristic symptoms leading in almost all cases, at least in all human cases and probably in all canine cases infected in the usual way, to death in from two to eight (or possibly ten) days. The organism causing this disease has not been isolated, but many of its characteristics are known. It is small enough to pass through the coarser Berkefeld filters. Many consider the characteristic Negri bodies found in the brain tissue to be forms of the parasite and point to the evidence of internal structure shown by the grouping of the granules within these bodies. The dog is the principal factor in the spread of rabies. Remlinger * tells us that the dog trans- mits the disease to man in 93% of the human cases. The virus is present in the saliva and is introduced by the teeth in biting, although it may be introduced into existing wounds. The virus may be present in the saliva for two or three days before the onset of definite symptoms, as has been shown by the experiments of Roux and Nocard. The most virulent tissues of a rabid animal are the brain and spinal cord. The peripheral nerves and several of the glandular structures (salivary glands, pancreas, lachrymal glands, suprarenal cap- sules, and rarely the mammary glands) are infec- tious, but other parts of the body do not contain the virus. Most of the period of incubation is taken up by the traveling of the virus along the nerves to the central nervous system and, as a result, the incubation period, when inoculation has been made into the extremities, is longer than when the virus has been introduced near the brain. METHODS OF DIAGNOSIS. The diagnosis of rabies in man or animals can usually be based, with a small percentage of error, on clinical symptoms alone when the disease has advanced to a point where marked symptoms are shown. After death, examination of the body does not reveal any gross chances sufficiently char- acteristic to warrant the making of a diagnosis. There is apt to be marked rigor mortis. In dogs the stomach frequently contains foreign bodies such as grass, sticks, and stones, but this may occur in other diseases. The only conclusive post-mortem evidence is found through microscopic examina- tion of nervous tissues. Important, chiefly ac con- firmatory evidence, are the multiplication of the cells of the endothelial capsule in certain of the nervous ganglia with more or less destruction of the ganglion cells. These lesions were described by Van Gehuchten and NPlis. Other changes of similar importance were described by Babis. They are the accumulations of newly formed cells around the ganglion cells in certain parts of the central nervous system. Of far greater practical importance are certain small round or oval bodies which were discovered and described by Negri and bear his name. They are found chiefly and characteristically within the ganglion cells of the brain, but frequently are seen away from those cells. The finding of Negri bodies alone is considered by the highest author- ities to be sufficient evidence on which to base the diagnosis of rabies. As a rule they are found most easily in the hippocampus but they can be dis- covered in other parts of the brain. The simplest way of demonstrating them, and the method used in most cases at the State Hygienic Laboratory, is to make, on glass coverslips, smears of gray matter from the hippocampus, and to stain \t.ith nneth!.lene blue and fuchsin according to the method of \I'il- liams. The coverslips are then mounted in bnliam and are carefully searched, for several hours if necessarv. Figure 3 shows photomicrogrnphs or preparations made in diagnostic work at the State Hygienic Laboratory. In the first picture is a large ganglion cell from the hippocampus from a dog's head which was sent to the laboratory from San Francisco. In each 324 CALIFORNIA. *STATE JOURNAL OF, MEDICINE Vol. X, No. 8 end of the cell is seen a large. round body. `. These are Negri bodies and are an indication that rabies is present. As already .stated, many suppose that the, Negri bodies are the actual pathogenic organisms ,j&rt tures pro a others ,consider them to be ,struc- E Fd by the:,+on, of .the toxin of rabies on tissue ce fis .`. The second picture is a photograph of a ganglion cell in a stained paraffin section from the hippocampus of one of the human cases which died in San Francisco. The Negri- body is shown in the protdplasm close to the cell nucleus. The third and, fourth pictures show free Negri bodies, one having the usual round shape `and granules, which are indistinct in the picture, and the other having the more unusual oval shape. `. Although Negri bodies, when found, are proof of the presence of rabies, failure to `demonstrate them does not completely rule. out the existence of the disease. The Negri bodies may be so .few or so small, either because the animal was killed early' in the disease or because of factors'which we do not know, that their detection is not accomplished in several hours' search. In order to be able to make an absolute diagnosis, which in many cases is very important to persons who have been bitten or who own animals which have .been bitten, it is necessary to inoculate brain tissue from the negative cases into laboratory animals, usually rabbits or guinea-pigs. The material in small quantity (0.1 to 0.2 c. c. of the suspension in physiological salt solution) can easily be injected through a small trephined opening into the space between the skull of the anesthetized animal and the brain. The animal should not be noticeably affected by this operation. If the brain tissue contains the virus of rabies, the animal will come down with the disease and exhibit symptoms in a varying length of time, usually 15 to 30 days in rabbits, although in some cases the incubation period is several months. The laboratory examination for diagnosis is car- ried on at several points in California. The State Board of Health does this work at its Hygienic Laboratory in Berkeley, when the specimens are properly iced in some watertight container and are sent by express prepaid. When the head arrives in the laboratory the top of the skull is removed and the. brain taken out. By dissection the hippo- campus is secured and smear preparations are made as already described. . It is advisable, when animals are under suspicion of having rabies, not to kill them if they can be safely captured and confined for a period of ten days. The symptoms usually develop rapidly and are in most cases sufficiently characteristic to leave no doubt, and at least to enable a decision with regard to the advisability of Pasteur treatment for any persons bitten. A decisive diagnosis is also important so that dogs which were bitten .by the suspected animal can be killed in order to prevent their developing the disease later and spreading it further. If the animal dies, the laboratory exam- ination is apt to be more conclusive than when it is killed early in the disease. TREATMENT OF RABIES. When the symptoms of rabies have once made their appearance, the disease cannot be checked and treatment is of no avail except for the amelioration of suffering. The agony of the few days of in- tense suffering can be lessened by careful protection of the patient from noises and drafts and, in the early stages of the disease, by the administra- tion of sedatives, but when the agonizing spasms are frequent and severe it is only humane to bring about relaxation and unconsciousness by means of ether or chloroform. In the absence of. a cure for rabies, the pre- ventive treatment becomes very important. Cauterization of the wound has been found through `long experience to diminish the chances of development of the disease, and this has been confirmed by experiment.. The most practical and efficient method of cauterization is the application of concentrated nitric. acid to the wound with a small stick or swab, as soon as possible after the biting. If the wounds are very large, as in the case of severe lacerations of the face, cauterization may be univise and it may be necessary to depend on careful washing with bland sterile solutions and the intensive Pasteur treatment. No method of cauterization saves a large enough percentage of cases to warrant the neglect of further preventive treatment. Fortunately, an efficient method of immunization was found for us by Pasteur. Soon after Pasteur began his studies on rabies he discovered that the virus' was located chiefly in the central nervous svstem, and, after failing to grow the microorganism of rabies on artificial culture media, he conceived the idea that it could be grown in pure culture in the living animal. He therefore inoculated the brains of rab- bits with brain tissue from rabid animals and kept his culture alive by transplanting it from rabbit to rabbit. The virulence for rabbits increased rapidly with these serial passages until the incubation period in rabbits became as short as six or seven days. Then no further change in virulence was apparent on further transplantation and the virus was known as fixed virus for rabbits, in contrast to the virus found in nature and called street virus. In several infectious diseases, for example, anthrax and chicken cholera, Pasteur had been able to produce immunity in animals by treating them with cultures of the infectious agent after the microtirganism had been rendered less virulent by being grown on artificial media under unfavor- able circumstances. Pasteur took the pure culture which he had produced for rabies, i. e., the spinal cords of rabbits which had just died of rabies, and attempted to render it less virulent in various ways, finally adopting as most practical a method of drying the cords in glass bottles over sticks of potassium hydroxide. After a cord has been dried in this way for eight days, it is no longer able to produce the disease, even in rabbits, which are specially susceptible to the fixed virus. Inocu- lation with such cords gives no symptoms but makes the person or animal inoculated resistant to a stronger virus, i. e., a cord which has dried a shorter time. By gradually increasing the strengths of the attenuated virus injected under the skin a considerable degree of immunity can be developed in an animal or person in from AUG., IgIz . CALIFORNIA STATE JOURNAL. OF MEDICINE 325 eighteen to twenty-one days. This immunity con- tinues to increase after treatment and as a rule reaches a high level fifteen .days after the end of treatment. In order, therefore, to give the highest protection, the Pasteur treatment must be begurr about thirty