ABSTRAcrs AND REPORTS.

INVESTIGATIONS REGARDING SO-CALLED FALSE RABIES (PSEUDOWUT).

AFTER summarising the literature on the subject, the author passes on to a consideration of the general features of the disease and of the virus.

Up to the present the disease has been observed in Hungary only, the animals affected being cattle, dogs, cats, and rats. \

The symptoms shown by cattle are persistent rubbing of the muffle, and more rarely of other parts of the body, producing bare bleeding patches surrounded by swollen and inflamed areas. The animals bellow and stamp with their hind feet. The appetite is for a time maintained, but tympanites soon sets in and the animals succumb to the disease within twenty-four to thirty· six hours.

Cats and' dogs are dull but re&tless and crouch in corners. There is a full flow of saliva but loss of appetite; vomiting and pharyngeal paralysis have been observed. In about half the cases observed the animals showed intense irritation of some part of the body, and by violent scratching produced in a few hours large abrasions of the skin, and even lesions of the deeper tissues. In some Clses symptoms of irritation are absent and the animals groan with pain. Breathing is laboured. As a rule there is unequal dilatation of the pupils, pupillary reflex is lost, and there are spasmodic muscular contrac;ions. There is no rise of temperature. Almost without exception death occurs within twenty-four to thirty-six hours, recovery having been observed in one case only, in a cat.

Among laboratory animals the rabbit and guinea-pig appear to be the most susceptible to the virus, rats and mice are less susceptible, and fowls and pigeons are resistant.

Intection may be transmitted by intraocular, subdural, intraperitoneal, intramuscular, and subcutaneous inoculation.

The period of incubation varies with the susceptibility of the animal, the virulence of the material, and the seat of inoculation, from thirty-six to ninety-six hours. Exceptionally it may be from five to eight days. After the period of incubation symptoms of restlessness, great excitement, and severe irritation set in. After subcutaneous inoculation there is inflam­malion and swelling of the skin and subcutaneous tissues at and around the seat of injection. The animals scratch, lick, and gnaw the place, or if they cannot reach it either with their mouth or claws attempt to rub it against some object. The irritation increases until the animals drop exhausted, and, showing frequent muscular spasms, die within a few hours. The duration of the disease from the onset of symptoms varies from three to thirty hours, generally six to ten.

The lesions found post-mortem are insignificant. The inflammation is often associated with hfemorrhage and necrosis at the seat of inoculation. Hyperfemia and ecchymoses of the central nervous system, meninges of the brain, and mucous membrane of the stomach and intestine are observed. The virus is always present in the nervous system, :;lnd almost always in the blood and vascular organs. The virus is not present in the bile, urine, or saliva. It does not pass through a Berkefeld filter.

The disease does not appear to be very contagious; healthy animals kept

ABSTRACTS AND REPORTS.

with infected ones do not become infected. According to Kern the infection under natural circumstances is conveyed by biting insects.

The brain remains virulent for two, and exceptionally for three, months when kept in glycerin. The virus does not appear to be easily destrnyed by disinfectants or heat.

Neither the bile of infected animals nor attenuated virus produces any immunity in rabbits.

The author tested the susceptibility of the small domesticated animals and various laboratory animals by feeding and inoculation.

I. Feeding Experiments. Dogs.-In this experiment three dogs were used. The first consumed in six days 1500 grammes of muscle from the hindquarters of a goat that had died of the disease. No symptoms whatever appeared. The second received about 300 grammes of the liver, spleen, and kidneys of the same goat without showing any symptoms. The third ate an entire guinea-pig that had died of typical false rabies, and showed no symptoms during' fourteen days"that it was under observation.

Cats.-Three YOUl'g cats were fed three times daily with mince made from the organs and muscles of rabbits dead of the disease, the mince being given in small quantities. By the fourth, fifth, and tenth days the animals were severely ill. The following were the symptoms presented: For some time before symptoms of the disease appeared there was a purulent discharge from the eyes. Up to this time the appetite was maintained, and the temperature varied within normal limits. With the onset of symptoms there was complete loss of appetite. The animals appeared apathetic and sat huddled up in corners with closed eyes, moaning from time to time. If removed from the cage they moved slowly and c!umsily, falling over every now and then, rising again painfully, and finally getting into a corner and remaining there. It was frequently observed that the animals slowly bent the head over the back, and sometimes so far that they fell over backwards. Two of the cats rolled on the floor at short intervals, while the third kept rubbing its head against the bars of the cage, and thus soon produced an inflammatory swelling around its eyes. There were frequent flexor spasms of the neck, and in two of the cats there was a marked flow of saliva. Towards the end the animals lay stretched out on the floor, the temperature fell below normal, and death occurred in twelve to twenty-four hours. No lesions could be discovered at the post-mortem.

In addition to these three cats, four rats were successfully infected by feeding, while the three dogs already mentioned, two rabbits, two guinea-pigs, one white rat, and eight white mice resisted infection in this way. Two of the infected rats died without having shown any symptoms, but the cause of death was proYfd by the inoculation of two rabbits.

Inoculation Experiments. Goat.-A goat was inoculated subcutaneously on the left side of the chest wall with an emulsion made of a piece of Ammon's horn from the brain of a dog dead of the disease. During the incubation period, which lasted six days, the animal was lame on the near fore leg, and there was some slight swelling at the seat cf inoculation. The goat showed symptoms of great excitement and restlessness, and sprang up suddenly, only to lie down again. Its gait was unsteady, the hind feet were stretched forward under the body, respiration was rarid and laboured, pulse rapid, and heart-beat full. It was continually biting, not the seat of inoculation but its left hock, and soon caused a bare excoriated patch. By repeated rubbing of its head against the wall it made excoriations around both its eyes. It became weaker, and finally lay extended on the floor, showing frequent muscular spasms. Death occurred after twelve hours' illness. An hour before death the animal's temperature rose to 40° C.

ABSTRACTS AND REPORTS.

At the post-JIlJrteJll typical lesions of septic~mia were found. At the seat of inoculation there was an abscess containing greyish-yellow odourless pus, and surrounded by a tough fibrous capsule. There was marked inflammation of the c~cum. The liver was enlarged, and showed at places punctiform h~morrhages. There was very pronounced swelling of the spleen and softening of its pulp. The epicardium was ecchymosed, and there was marked congestion of the brain and its membranes.

Sheep.-Inoculated subcutaneously with 1 cc. of brain emulsion from a guinea-pig dtad of typical false rabies. Incubation period five days. Irritation of the seat of inoculation, muco-serous discharge from the eyes and nose, and diarrhcea. Death after one day's illness. Except for severe inflammation at the seat of inoculation there were no lesions discoverable. It is doubtful whether this animal died of the di;ease, as inoculations of its brain substance into rabbits, guinea-pigs, and white mice failed to infect.

Cat.-A cat inoculated intramuscularly with 1 cc. of brain emulsion from a rabbit dead of the disease showed symptoms on the third day. Death occurred during the following night. Beyond local lesions at the seat of inoculation none were found.

Dogs.-The majority of the dogs were inoculated subcutaneously, but in a few cases the inoculation was either intramuscular or intraocular. After subcutaneous and intramuscular inoculation the period of incubation was, as a rule, from three to four days, and, exceptionally, six or seven. After intraocular inoculation the period was two days. The duration of the disease varied from twe\ve to twenty-four hours, and in one case was three days.

At first the animals were restless and constantly licking the seat of inoculation. This was followed by biting and gnawing, and accompanied by howling. The dogs showed a tendency to bite foreign bodies, such as wood or glass, that were held out to them, but in no case was any aggressive­ness observed. The stage of irritation was followed by exhaustion, the animals lying groaning on the ground. In some cases there was a muco­purulent discharge from the eyes and a voluminous secretion of saliva. Vomiting was also observed. There were cramp-like contractions of the muscles of the extremities and jaw, breathing became shallower, and death occurred.

Intraocular inoculation was promptly followed by a flow of tears. The affected eye was kept closed, and there was soon a severe keratitis and conjunctivitis, accompanied by a copious disch3.rge of muco-purulent material. Irritation commenced and the whole side of the head was soon raw and bleeding on account of persistent rubbing and scratching.

In the last stages there was dulness and exhaustion. There was complete loss of appetite from the onset of symptoms, but some

animals drank water during the period of illness. The temperature was very variable in different cases. In some there was

a rise to 39'5° C. only, and in others it rose to 41° and 42°. Before death the temperature fell to 36° or a little over. With the exception of the swelling and inflammation at the seat of inoculation no lesions were found at the post­mortem in one series of cases. In some animals abscesses up to the size of the palm of one's hand formed. These contained either a chocolate-coloured or a thick yellowish-white pus-like material. In some cases the stomach and i.ltestines were markedly congested and the bladder full to distension.

The susceptibility of the dog to the virus does not appear to be certain. Although ten dogs were infected with comparatively large quantities of virulent brain substance only five were infected by the first inoculation. Two were infected after the second, and two after the third, inoculation. One dng which had been inoculated three times was only infected by a fourth, which was intraocular. It is not definitely settled whether repeated inocula-

ABSTRACTS AND REPORTS.

tion with virus confers any degree of immunity. The fact that in one dog which was twice inoculated the period of incubation was seven days, and the duration of the illness three days, suggests this possibility.

2. Experiments with Laboratory Animals. Rabbits.-In the majority of cases the inoculation was either subcutaneous or intramuscular. Occasion­ally intraperitoneal, subdural, and intraocular inoculations were made.

The period of incubation following the first three of these varied from two to four days, and after the latter two from one and a half to two days. The average duration of the disease was five to fifteen hours.

In the majority of cas::s there was evidence of inflammation at the seat of inoculation within twelve to twenty-four hours. In the case of some of the animals inoculated into the muscles of the hind limb the seat of inoculation was not scratched or bitten but the distal extremity of the limb or the flank. In the intervals of biting the affected parts the animals took up unnatural positions. In animals inoculated on the abdominal wall or into the muscles of the hind limbs the position taken up was either on the back or side with the legs and head stretched out, the animal commencing after a time to bite itself again. Then, as in other cases, exhaustion set in and the animals lay down breathing slowly and laboriously. Muscular contractions occurred in all parts of the body.

In many cases rabbits which appeared to be perfectly well in the evening died during the night without any clinical observation being possible. A great number showed no lesions due to biting the seat of inoculation, and in these cases diagnosis was made by further inoculations of rabbits.

It frequently happened that animals inoculated with certainly virulent material showed no symptoms of irritation. They were dull and apathetic, and died after an illness of ten to twelve hours without showing any clinical -symptoms. In every case further inoculations showed that the animals had died from false rabies.

In animals inoculated intraperitoneally there was in no instance any evidence of restlessness, vomiting, or irritation.

Animals infected by subdural inoculation, on the other hand, always showed characteristic symptoms.

At the commencement of the disease they remained quite quiet for a time, and then suddenly began to lift their noses up and bend their heads over backwards, in some cases to an extent sufficient to cause them to fall over. These symptoms were repeated with increasing frequency. After an attack of this sort the animals remained quite quiet as before its occurrence. Some of the rabbits inoculated in this way evinced an irresistible tendency to run into the walls of their cages or any object placed in their way. With the onset of paralysis the symptoms of irritation generally ceased, death occurring soon after.

After intraocular inoculation the outstanding symptoms were photophobia, a muco-purulent discharge, marked keratitis and conjunctivitis, and persistent scratching and rubbing of the affected eye or the side of the face.

The lesions found at the post-mortem were, save for the local lesions, insignificant. In cases in which the inoculation was subcutaneous there was inflammation to a varying degree.

After intramuscular inoculation there was evidence of severe inflammation, and in many cases the dose of virus was found at the seat of inoculation apparently unaltered. As a rule, there were no visible lesions in the internal -organs. In several cases the brain was congested, but there was no <:edema.

On a number of occasions it was observed that rabbits inoculated with brain substance from dogs suffering from the disease remained perfectly healthy, and that inoculation of dogs with material from affected rabbits was not always successful the first time.

ABSTRACTS AND REPORTS.

Guineap(s>s.-Although a large number of guinea-pigs of various ages were inoculated the symptoms of the disease appeared in a comparatively small proportion only. Rabbits inoculated with the same material became infected. Of the guinea· pigs that contracted the disease some died before symptoms appeared, and in others the disease ran the usual course.

Af[er subcutaneous and intramuscular inoculation the period of incubation varied from two to eight days, and after subdural inoculation from twelve to eighteen hours. At the post-mortem the only lesion generally found was inflammation at the seat of inoculation.

Rats. -Rats were found to be susceptible by subdural inoculation only. The period of incubation varied from two to three days, and the period of illness from twelve to eighteen hours. The symptoms were the same as in rabbits, and no lesions were found at the post-mortem. Mice, fowls, and pigeons resisted inoculation.

Distribution of the Virus in the Body.-Experiments with defibrinated blood, blood-serum, and urine showed that these contained the virus. On the other hand, it could not be demonstrated in bile or saliva. One experiment showed that in a pregnant rabbit affected with the disease the virus passes into the brains of the fa!tuses.

Resistance 0./ the Virus. Resistance to drying. The virus was found to be destroyed by drying for forty-nine days at room temperature, eleven days at 25 ° c., and eight days in a exsiccator.

Resistance offered by the virus to putrefaction and to preservatives at different temperatures. Brain emulsions exposed to putrefaction for eleven to twenty-five days at room temperature produced no illness in guinea-pigs. Experiments with rabbits showed that after eleven days under these con­ditions the decrease in virulence was slight, but that after twenty-five days it was pronounced. Emulsions left at room temperature or in an incubator at 3 f c. for twenty-eight days failed to transmit the disease to rabbits. In an ice-chest the virulence was maintained for eight weeks. Brain substance preserved in glycerine retained its virulence for eight months in an ice-chest, and blood-serum for eight or nine weeks.

Resistance to heat. 60° C. dry heat for thirty minutes destroyed the virus, as did 70° C. for ten minutes. Over the open flame the virus was destroyed in an instant. Over a water-bath the virulence of blood-serum was destroyed in sixty minutes at 55° c., in thirty minutes at 58° c., and fifteen minutes at 60° C.

Resistance to disinfectants. Exposure for five minutes to I per cent. anti­formin, 5 per cent. kreolin, and I per cent. sublimate solution did not suffice to kill the virus, but exposure for five minutes to 5 per cent. antiformin, 10

per cent. kreolin, 2 per cent. sublimate, and 3 per cent. carbolic acid rendered it innocuous.

Contagiousness.-On several occasions infected animals were caged with sound ones, but in no instance were the sound animals infected. .

Filtrability.-Four experiments were carried out, . but in no case did the filtrate prove virulent.

Immunity.-lt was not found possible to confer any immunity by using either brain substance or blood-serum the virus of which had been attenuated or destroyed. (Zwick and Zeller, Arbeiten a. d. Kaiser!. Gesundheitsamte, Vol. XXXVI., NO.3, Feb. 19II, pp. 382-408.)