The saliva of rabid Herbivora and Omnivora, long held to be harmless, is now known to be virulent. Berndt has successfully inoculated it from an ox to four sheep; Eckel from a goat to a sheep; Rey from sheep to sheep; Lessona from an ox to two horses and a sheep; Tombaro from a heifer to a sheep, a horse, and two dogs; Youatt from horse and ox respectively to dogs; Ashburner from an ox to fowls; King from a cow to fowls; and Majendie, Breschet, Eckel, Hertwig, and Renault from man to dog; and Earle from man to rabbits. Besides these are a series of accidental cases, as from horse to man (Youatt), from a sheep to its shepherd (Tardieu), and from man to man (Aurelianus, Enaux, Chaussier).
Experiments by Hertwig and Eckel seem to show that saliva loses its virulence on the supervention of cadaveric rigidity or putrefaction in the dead body. Haubner even believed dried saliva to be innocuous. Yet Count Salm successfully inoculated the dried saliva of a rabid dog, and Schenkius reports a case of hydrophobia produced by a scratch of a hunting-knife that had been used to kill a mad dog some years before. A veterinary student at Copenhagen cut his finger while dissecting the body of a rabid dog twelve hours after death, and died of hydrophobia six weeks later. These cases in man may, it is true, have resulted from fear, but the same cannot be said of the infection of hound after hound placed in empty infected kennels, as recorded by Blaine, Youatt, and others. In the face of this it would require very strong negative testimony, indeed, to prove that the virus of rabies is devitalized in drying—a process which prolongs the vitality of other virulent matters.
Up to the present time the germ of rabies has not been demonstrated. That it is a particulate living organism may be reasonably deduced from its power of indefinite increase—a quality possessed by no mere chemical nor mechanical agent, also from the saliva proving non-virulent after filtration through plaster, while the solid residue left on the filter was virulent (Bert). But, although bacteria have been found in the saliva, those demonstrated up to the present are manifestly ordinary aërial bacteria, such as in Pasteur's experiments produced septicæmia rather than rabies. It still remains, therefore, for some future observer to discover that germ of which we cannot doubt the existence.
The point of election of this germ appears to be mainly the nervous tissue. Pasteur found the brain-matter of rabid animals invariably infectious, and has preserved the moist brain in an infecting condition for three weeks at a temperature of 12° C. He found that by direct inoculation in the brain-substance the period of incubation was abridged, rabies often showing itself in six, eight, or ten days. In the face of Rossi's successful inoculation of nerves and Pasteur's results with brain-matter it is difficult to account for the unsuccessful inoculation of nerve-tissue in six successive experiments by Hertwig. It seems to show that though the virus is concentrated in the brain, and especially in the medulla and pons, yet it does not equally permeate the entire nervous system. This election of the poison for the nervous tissue led Dr. Douboue in 1851 to advance the theory that it is propagated from the seat of inoculation to the brain through the medium of the nerves—a position now assumed by Pasteur. This, we fear, is not well founded. The poison, advancing for a month or more along the lines of the nerves, would probably derange and abolish their functions, as it does so speedily and effectually that of the nerve-centres after it has gained a seat in them, whereas, in reality, the local paralysis only appears in the last stages and after the symptoms of cerebral disorder are well established. Furthermore, a common premonitory symptom of rabies is congestion, swelling, and irritation of the inoculation wound, showing a sudden extraordinary activity at that point as a herald, if not a condition, of the general infection, whereas under a slow propagation along the nerves from the first this irritation would probably have been greatest in the wound at the outset, and would have thereafter kept pace with the progress of the virus along the nerves. Again, the blood is not always infecting. Blaine, Youatt, and others of the older observers had no fear of the blood. Hertwig obtained rabies in two cases only out of eleven inoculations with the blood of rabid subjects. The blood in this, as in some other diseases (variola equina, v. ovina, lung plague of cattle), proves to a certain extent inimical and destructive to the poison. Galtier inoculated nine sheep and one goat by intravenous injection of the saliva of mad dogs, in no case with fatal results nor indeed with any manifestation of rabies, but with the effect of fortifying the system so, that subsequent inoculation into the tissues of the saliva of rabid animals was harmless. Test inoculations made in the tissues of other animals with the same virus used in his intravenous injections, and his subsequent inoculations of the animals so treated, invariably determined rabies. Pasteur repeated these intravenous injections in dogs with the result of rapidly inducing rabies in a fair proportion of cases. One of his cases produced in this way recovered, and thenceforward resisted all further inoculation with the virus. Others that did not perish from intravenous injection afterward died of rabies after inoculation in the brain. Unfortunately, neither Galtier nor Pasteur have reported how much virulent saliva was injected in any one case, so that we have no data as to whether the difference was due to the varying quantity of the virus introduced in the various cases. Lussana, an Italian physician, had already in 1878 experimented on two dogs by injecting into their veins the blood of a physician who died of hydrophobia. The blood was drawn by leeches and cupping-glasses, and five grammes were injected into each dog. One died on the twenty-fourth day, presenting the symptoms and post-mortem appearances of rabies. The second at the end of one hundred and forty days developed symptoms of rabies which lasted a month, when the animal was sacrificed, and nothing special found at the autopsy. The data do not warrant a very positive conclusion, yet they seem to imply that the receptivity on the part of the dog is greater than that of the small ruminants. They suggest, further, a greater relative potency in the battle for life of the blood-globules of the small ruminants with this unknown rabific germ. This antagonism between the blood of the ruminant and the germ of rabies finds a parallel in the case of other disease-poisons in their relations to the nuclei of the tissues. Thus animals may prove refractory to a small dose of the poison of anthrax, yet Chauveau has shown that this virus will overcome all native or acquired insusceptibility when administered in excess. The same is true of the poison of chicken cholera, which Salmon dilutes until it is non-fatal, though still affecting the system and conferring an immunity from its attacks in the future. So with the lymph of variola ovina, which Peuch diluted to 1/50 and injected with the effect of producing slight fever and immunity without vesiculation.
This view would imply that in ordinary cases (inoculation with a moderate amount of the poison) the virus is for a time localized in the vicinity of the wound; and this is further supported by the fact that thorough excision and cauterization of the wound some time after it has been received is still often protective. It is weakened by the fact that bites of dogs in the stage of incubation sometimes produce rabies, but it must be borne in mind that there is still a period between the passage of the living germ to the salivary glands and brain and the growth of the germ in the nerve-centres, so as to produce pathognomonic symptoms, during which both blood and saliva must be virulent.
The ratio of successful inoculations to the bites is very varied. Thus, out of 555 dogs reported to have been bitten by rabid dogs, 188 contracted rabies; out of 183 experimentally exposed till bitten or inoculated, 91 became mad; out of 73 cattle bitten, 45 became rabid; out of 121 sheep bitten, 51 succumbed; and of 890 persons bitten, 428 took hydrophobia (48 per cent.). Of 440 bitten by rabid wolves, 291, or 66 per cent., took the disease. Such statistics are, however, far from satisfactory. Of dogs reported mad, some have only suffered from epilepsy, convulsions, or colic, while of those bitten by the really mad dog, some have sustained simple bruises without any real abrasion; in other cases the teeth have been wiped clean by passing through thick wool, hair, or clothing, or even the flesh of other animals just bitten; in other cases the bite has been inflicted at a time when the virulence of the saliva was at its minimum, or in a subject which was naturally insusceptible. The protective effect of clothing was well illustrated in a case which came under my notice in London. Six animals bitten by a rabid dog all contracted rabies, whilst a man bitten a few hours before through the coat-sleeve, and who did not have the wound cauterized for a full hour after the bite, escaped. Bouley found that in 32 persons bitten in the face, 29 died of rabies (90 per cent.); of 73 bitten on the hands, 46 died (63 per cent.); of 28 bitten on the arms, 8 died (28 per cent.); of 24 bitten on the lower limbs, 7 died (29 per cent.); of 19 bitten on the body (usually multiple wounds), 12 died (63 per cent.). The high mortality from the bites of rabid wolves and skunks is mainly due to this habit of attacking the face and hands. As illustrative of insusceptibility may be quoted the poodle of Hertwig, which was inoculated nine times with unquestionably rabic virus without effect; also the pointer of Rey, which was seventeen times bitten by rabid dogs without harm; also the acquired immunity of Galtier's sheep and rabbits, above referred to.
INCUBATION.—In the dog this varies from 6 days (Pasteur) to 240 days (Bollinger). In the majority of cases it ends in from 20 to 50 days. Pasteur, by inoculating into the brain substance direct, reduced the incubation from 20 days to 6 days. In the horse the limits of reported cases are from 15 days to 92 days. In the ox incubation varies from 20 to 30 days; in sheep, from 20 to 74 days; and in swine, from 20 to 49 days in recorded cases.
In man incubation is believed to be often much more prolonged. In 6 per cent. of all cases it is from 3 to 18 days; in 60 per cent., from 18 to 64 days; and in 34 per cent. it exceeds 64 days (Hamilton, Thamhayn). Quite frequently symptoms of hydrophobia appear from three to six months after the bite; in a few the period is prolonged to one or two years, and in rare instances to seven (Schule), and even twelve years (Chabert). But all such cases of prolonged incubation in man are at the least extremely doubtful. Man often contracts a pseudo-hydrophobia as the result of fear, and is curable by moral suasion alone; and as no such protracted incubations are noticed in the lower animals, and as no one of these abnormally deferred attacks in man has been verified by successful inoculation on animals, it is prudent to reserve a full assent until they are supported by better testimony. A specimen of such cases is that recorded by Chirac, in which a cadet bitten at Montpellier afterward spent ten years in Holland, and then, returning and hearing that his fellow-cadet bitten by the same dog had died of hydrophobia, he also manifested the disease and died. Another is the case of a man who, after having been bitten, spent two years in prison, and then developed hydrophobia and died. A mind naturally erratic and rendered weaker and more susceptible by prolonged confinement would prey upon itself and exaggerate the danger when the subject had been forcibly presented. In all such cases the attending physician should feel bound in the interests of humanity to inoculate a dog or other animal and ascertain whether or not the disease is virulent. The value of such results in dealing with future cases of the same kind cannot be overestimated.
The period of incubation appears to be relatively shorter in the young (average 45 days) than the old (average 70 days), and is believed to be shortened by constitutional excitement from violent passion, fever, the heat of the weather, or electrical disturbances.
During incubation no sign of the disease can be detected; it is even said that the wounds heal with unusual rapidity; but it is certain that toward the end of the latency the cicatrix, alike in man and animals, tends to become sensitive, itchy, congested, and even the seat of papular eruptions. The vesicles (lyssi) which, according to Xanthos, Marochetti, and Magistel, appear near the opening of the sublingual glands within a few days (6 to 20) after inoculation, have not been found by any recent observer.