Chapter 32

After a period ranging from weeks to years, tubercles rise from the spots described, varying in size from a pea to that of a nut, and they may be as large as a tomato. They are in color, yellowish, reddish-brown, or bronzed, often shining as if varnished or oiled, are covered with a soft, natural, or slightly scaling outer skin, roundish or irregular in shape and are isolated or grouped numbers of very small and ill-determined nodules may often be seen by careful examination of the skin in the vicinity of those that are developed. They may run together and cause broad infiltrations and from this surface new nodules spring. They may be in the skin or under the skin and feel soft or firm. The eruption of these tubercles is usually preceded at the onset by fever, as well as by puffy swelling of the involved region, eyelids, ears, etc. These leprous tubercles choose the face as their favored site. They mass here in great numbers, and thus produce the characteristic deformity of the countenance that has given to the disease one of its names, Leontiasis (lion face).

In such faces the tubercles arrange themselves in parallel series above the brows down to the nose, over the cheeks, lips and chin, and as a result of the infiltration and development of the conditions the brows deeply over-hang; the globes of the eyes, and the ears, are so studded with tubercular masses as to stand out from the side of the head. The trunk and extremities, including the palms of the hands and soles of the feet, are then usually involved to a less degree. The arm-pit, genital and mammary regions, and more rarely the neck and the palms of the hands and soles of the feet, may be invaded. In occasional cases when the development of tubercles upon the face and ears is extensive, there may not be more than from five to fifty upon the rest of the body, and these either widely scattered and isolated or agglomerated in a single hard, flat, elevated plaque of infiltration upon the elbow or thigh. When the tubercles run together (become confluent) large plaques of infiltration may form, which are elevated and brownish or blackish in color.

The soft palate and larynx are often involved when the skin lesions are present. The voice may sound gruff and hoarse, and the tongue, the larynx and soft palate have been found studded with small sized, ashen-hued tubercles. These tumors or tubercles may degenerate and form into irregularly outlined, sharply cut, glazed ulcers, with a bloody or sloughing floor, or they may disappear and leave behind pigmented, shrunken depressions, or they lose their shapes from partial resorption. A large plaque may flatten in the center until an annular disk is left to show its former location. Coincident symptoms are disturbance in the functions of the sweat and sebaceous secretion, thinning and loss of hair in the regions involved, especially the eyebrows, and disorders of sensibility. Later results, are a nasal catarrh, atrophy of the sexual organs in both sexes, with impairment or loss of procreative power, hopeless blindness. However the course of the disease is very slow, and years may elapse before these several changes are accomplished. Often the disease appears quiescent for months at a time, after which fever occurs and with it acute or sub-acute manifestations appear, including gland disease, orchitis, ulcerative processes, slow or rapid, followed by gangrene and a relatively rapid progress is made toward a fatal conclusion.

Toward the last the mutilations effected by the disease may result. Parts of the fingers or toes, whole fingers or toes, and entire hand or foot may become wholly or partially detached by the ulcerative and other degenerations. This stage of this type of the disease may extend through ten or more years. After it has fully developed the dejected countenance of the leper, with his leonine expression and general appearance is highly characteristic.

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LEPRA MACULOSA.--This form is more common in tropical countries and is distinguished chiefly by its macular (spotty) lesions. In size they vary from a small coin to areas as large as a platter. They are diffused or circumscribed, roundish or shaped irregularly, yellowish, brownish or bronzed in color, often shiny or glazed. They may be infiltrated and may be elevated, or on a level with the adjacent tissues. The patches are usually at first very sensitive, but they finally become insensitive, so that a knife can be thrust deeply into them without being felt. The regions chiefly affected by this type are the back, exposed parts, the backs of the hands and wrists, the forehead, the cheeks, ears, back of the feet, and ankles. The eruptions may be scanty or general; conspicuous or insignificant. The eruptive symptoms are associated commonly, early or late, with the serious phenomena described below.

LEPRA ANAESTHETICA. (Nerve Leprosy. Atrophic Leprosy. Lepra Trophoneurotica).--Before the development of this form of leprosy there may be one or two years of ill-health. Usually the skin at this time becomes in localized patches over-sensitive, sometimes there is over-sensitiveness and special nerves, because of their enlargement, become accessible to the touch. Those named later become tender, and the seat of lancinating or shooting pains. This clinical variety may be commingled in its symptoms with each of the other types. With or without such commingling, however, there commonly is noted, after exposure to cold or after being subject to chills first an eruption, red (erythematous) patches, or of "bullae," size of a bean on cheeks, ears, back of the feet, and ankles. The eruption may be outer skin covering (epidermis) and filled with a clear tinted or blood-mixed serum, and usually occurring upon the extremities. The scars that follow are shrunken (atrophic) patches, each often greater in extent than the base of the original trouble, color whitish, shiny, glazed, or better described as a tint suggesting the hue of mica; their outline is circular and form also the dumb-bell figure by running (coalescing) together, or juxtaposition. These scars are always without sensitiveness (anaesthetic), and they may exist together with spotted and non-sensitive patches upon the trunk or other parts such as the face, hands, feet, ankles, thighs, but rarely on the palms and soles. Neither those of the one class nor of the other, however, are disposed over the surface of the body in lines, bands or curves, corresponding with the distribution of the skin (cutaneous) nerves. Sometimes the ulnar and other nerves (median, posterior tibial, peroneal, facial and radial) that are accessible to the touch are swollen, tender, insensitive or as rigid as hardened cords. Reddish-gray swellings may be recognized by the eye along the nerve tract. General shrinking skin symptoms follow. The skin becomes dry and harsh; there is little or no sebaceous product and the skin of the face seems tightly drawn over the bones. As a consequence of deforming shrinking (atrophy) of the eyelids, a persistent overflow of tears, consequent eye changes follow, and a constant flow of saliva escapes from the parted lips. The fingers are half drawn into the palm of the hands; the nails are distorted and ulceration occurs later. These ulcers are irregular, oval, roundish or linear in form covered with thin blackish, flattened, tenacious crusts with soft bases, and their floors covered with a soft debris mixed with blood, the whole insensitive to every foreign body, and external application. At last the symptoms of mutilating lepra (leprosy) may occur, digits or portions of the wrist, part of hand (meta carpus) or corresponding portions of the foot may be detached from the body. Death may occur at any time during the course of the disease. In this form it is said to last from eighteen to twenty years and is thus not so rapidly fatal as the tubercular variety.

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Treatment.--The main treatment is the isolation and segregation of all lepers from contact with the well; wholesome laws are enforced in some countries where leprosy prevails, and provision is made not only for the isolation and segregation, but also for their care. On account of its relative variety America has not yet awakened and legislation only forbids the entry of infected persons. At Molokai, in the Hawaiian Islands, provision is made for the care of lepers. Many of the public hospitals for the care of the sick poor refuse to receive lepers. The child of a leprous woman should be removed from the mother after birth and not nursed by another woman. No medicines are known to have any curative effect. An immediate change of residence and climate should be made if the patient happens to live in a district where the disease prevails. A highly nutritious diet should be taken.

The outlook.--The future is in general dark for the leper. It is often of a malignant character, and a fatal result is the rule. A change of climate and conditions may help. Scandinavian lepers who have removed to the United States have been greatly benefited by the change, but there is no known cure. The isolation should be as effective as that for tuberculosis. It is not contagious but infectious.

HYDROPHOBIA.--Rabies and hydrophobia are two different terms, meaning the same disease, the former meaning to rage or become mad. This term applies more especially to the disease as it exists in the maniacal form in the lower animals, while hydrophobia comes from the Greek, meaning "dread of water." As we occasionally find this dread of water only in the human subject, the term is properly used in such a case. The lower animals frequently attempt to drink water even though the act brings on a spasmodic contraction of the swallowing (deglutitory) muscles. Hydrophobia is an acute infectious disease communicated to man by the bite of an animal suffering from rabies. It is due to a definite specific virus which is transmitted through the saliva by the bite of a rabid animal. Its natural habitat (location) is the nervous system, and it does not retain its virulence when introduced into any other system of organs. It is essentially a nervous disease and transmitted by the saliva of rabid animals. When inoculated into a wound this virus must come in contact with a broken nerve trunk in order to survive and reproduce itself. If by accident it attacks the end of the broken nerve trunk, it slowly and gradually extends to the higher nerve centers and eventually produces the disease.

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The incubation, or the time it takes for the disease to develop, varies, but usually is from three to six months. There is a recorded case where the person began to show symptoms of the disease thirteen days after having received a severe wound on the head. The incubation period is seldom longer than six months. The symptoms of the disease in the human being vary within narrow limits. There are three classic symptoms usually encountered, and these are fear, apprehension or excitement, together with deglutitory (swallowing) spasms, terminating in general paralysis. The patient remains conscious of his agony to the end, but the period of illness is of short duration, lasting from one to three days.

The bites of rabid dogs cause ninety per cent of the cases in man and animals. The cat is the next important factor in spreading the disease and about six per cent of the cases are caused by this animal. For other cases four per cent come from bites of horses, wolves, foxes, etc. The wolf in Russia, or other animals like it, may be the chief cause there; but dogs cause ninety per cent, taking all the cases found. Man, dog, cat, horse, cattle, sheep, goat, hog, deer, etc., are subject to the disease either naturally or experimentally. The disease is confined commonly to dogs, because the dog naturally attacks animals of his own species and thus keeps the disease limited mainly to his own kind. Naturally the dog follows this rule, but on the other hand, in the latter stages of the disease he usually goes to the other extreme and even attacks his own master, etc. The dogs that are the most dangerous and do the greatest damage are of the vicious breeds.

The rabbit or guinea pig is used for demonstration in the laboratory. Guinea pigs respond to the virus more rapidly than do other animals and therefore they are especially useful in diagnostic work. Rabbits, however, on account of the convenient size and ease with which they are operated upon, are usually the choice in the production of material used in treating patients.

The director of one Pasteur Institute says, "We have two classes of patients to deal with in the Pasteur institute. The larger class, of course, are those inoculated by the bite of rabid animals, but we also have a few who are infected by the rabid saliva accidentally coming in contact with wounds already produced. In these accidental eases the disease is almost as likely to result as in those to whom the virus is directly communicated by the bite." The wounds considered most dangerous are the recent fresh wounds. The possibility of infection decreases with the formation of the new connective tissue which protects the ends of the broken nerve fibres. One must remember, however, that wounds over joints, especially on the hands, are likely to remain open for some time. A dog ill of this disease can give the disease to man through licking a wound. Such a case has been recorded. This dog licked the child's hands before it was known to be mad. The child died from the disease. As stated before ninety per cent of the cases are inoculated by the bites of rabid animals.

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The wounds are considered according to their severity and location. Lacerating, tearing wounds upon uncovered surfaces, especially the head, are the most dangerous. This is due to the fact of the closeness of the brain and the large amount of infection in such a wound, and for this reason treatment should be immediately given. But smaller wounds should also be treated for the smallness of the wound furnishes no sure criterion as to the future outcome of the disease. All possible infections should be regarded as dangerous when considering the advisability of taking the Pasteur Treatment. The small wound has usually a longer period of incubation, because of the small amount of infection, still it may cause a fatal termination. A dog never develops rabies from a lack of water or from being confined or overheated during the summer months. A spontaneous case of rabies has never been known. It must be transmitted from animal to animal and the history of the case will point to a previous infection by a diseased animal.

Where rigid quarantine rules exist the disease does not occur. In Australia they quarantine every dog, that comes to that country, for six months, and in consequence they have never had a case of rabies. In Russia they have had many cases. In Constantinople the disease frequently "runs riot." France has lost as many as 2,500 dogs in one year. Before the Pasteur Treatment was instituted (in 1885) there was an average of sixty deaths in human beings in the Paris hospitals.

Belgium and Austria average one thousand dogs annually. There was a yearly average in Germany of four hundred dogs, dying of rabies, until the law requiring the muzzling of dogs was strictly enforced and since that time the disease is practically unknown. We do not have strict quarantine laws against dogs, and the result is death from hydrophobia in many states annually. It was formerly believed that rabies was a hot weather disease. The number of cases during the winter months of late years has disproved that belief, for the records of the institute for treatment of hydrophobia at Ann Arbor have shown a decrease of cases during the summer months. This was before 1908. This shows that rabies is not a hot weather disease.

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Ordinarily cases of rabies occur here and there (sporadic), but if the conditions are favorable epidemics break out. One dog may bite several dogs and these dogs bite others and thus spread the disease to many. Not every animal bitten by a mad dog develops the disease. The disease does not always follow the bite. Only about forty per cent of all animals bitten by a mad dog contract the disease. This is given by a noted authority. Statistics also show that in man the disease develops in only about twenty per cent of the cases in those who have been bitten by rabid dogs. But in dealing with those who have been bitten such measures should be taken as would be if they were certain of developing the disease; one cannot tell how much poison enters the system in such cases and preventive procedures should be taken. There are reasons why everyone who is bitten does not contract the disease.

The location and character of the bite must be considered. Bites on the head, neck and hands have been recognized as more dangerous, from early times, and such bites produce fatal results quicker than do bites on other parts of the body, and the reason is largely due to the fact that the other parts of the body are more or less protected by the clothing, and this clothing prevents the entrance of so much poison into the system. Bites on the head give a high mortality rate and are rapidly fatal. The close proximity to the brain is one reason.

The part the clothing plays in protection is clearly shown by the following quotation from an eminent authority: "In India where the natives dress very scantily, the mortality was exceedingly high up to a few years ago, at which time the British introduced the Pasteur laboratories. The clothing protects the body and it holds back the saliva and can be looked upon as a means of filtering the saliva of the rabid animal, most of the saliva is held back as the teeth pierce the clothing, so that upon entering the flesh the teeth are practically dry, and only a portion of the virus is introduced. Upon entering the wound this small amount of virus is further diluted by the tissue juices to the non-infectious point. We know from actual experimental work in the laboratory that the higher dilution will not kill."

If a portion of the brain of an animal dead from street virus is taken and made up in a dilution of one to five hundred, and this is injected, we find that it does not produce death. But a dilution of one to three hundred will invariably kill. This is practically what very often happens when one is bitten through the clothing. The saliva may be filtered and held back so that a small amount is introduced; perhaps a dilution of one to five hundred of the virus may get into the wound, but this is usually not enough to cause the disease. There is no possible way of estimating the amount of the inoculation. In such cases one's chances of never contracting the disease are only decreased; that is all we can say.

The treating of individuals, bitten by rabid animals, in the Pasteur Institutes, is simply the practical application of results obtained by Pasteur from his original work on rabies virus. Pasteur was a French chemist living in Paris, and he began his search for the cause and cure of rabies in 1880. He hoped to find a sure method of preventing the development of the dread disease, even if he could not find a cure for it after it had developed. While he was pursuing this research Pasteur had access to the cases of rabies in the Paris hospitals, and these numbered sixty each year. He had practically an unlimited supply, for France could furnish him with twenty-five hundred more mad dogs, and a large number of other animals each year.

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Pasteur devoted the remainder of his life to the study of this subject. He collected some saliva from the mouth of a child, on December 11, 1880, who had died at the Hospital Trousseau four hours before. This saliva he diluted with distilled water, and this mixture he injected into rabbits, and they all died, and the saliva taken from these rabbits when injected into other rabbits caused their death with rabies. He found also that saliva from rabid dogs almost always caused the disease. The incubation period varied within wide limits, and very often the animals lived. He then used the blood of rabid dogs for inoculation, but these blood inoculations always failed to produce the disease. Pasteur was convinced after careful study of rabid animals during the many months necessary to complete his experiments, that rabies was a disease of the nervous system, and that the poison (virus) was transmitted from the wound to the brain by the way of the nerve trunks. Then to prove his theory Pasteur removed a portion of the brain of a dog that had died of rabies. A part of this was rubbed up in sterile water and used to inoculate other animals; and subcutaneous inoculations with this material almost always produced death.

After this Pasteur tried a new method and injected directly into the nervous system, either into the nerve trunk or directly into the brain, after trephining, and all such injections produced rabies in the injected animal and death. He also found that rabbits inoculated in the brain always died in the same length of time. When he injected into the nerve trunk the inoculation period was longer, depending upon the distance from the brain. Two problems now remained for Pasteur to solve, and these were, how could he obtain the definite virulence and how could he reduce the virulence regularly and gradually, so that it could be used by inoculation safely as a vaccine to produce immunity to rabies in healthy animals, and also to prevent the development of rabies in animals bitten by rabid animals. He first tried successive inoculations. These inoculations were made, after trephining, directly to the brain, and he used a portion of the brain as a virus each time. He inoculated rabbit number one with a portion of brain taken from a rabid dog, and this rabbit died on the fifteenth day. He then inoculated rabbit number two with a portion of the brain of rabbit number one; from the brain of rabbit number two the virus was supplied for inoculating rabbit number three, and thus the brain of each inoculated rabbit was taken, after its death, for material to inoculate the next rabbit in the series. This experimentation showed him that each rabbit in the series died a little sooner, showing that the virus was becoming more virulent, till no increase in activity of the poison was shown after the fiftieth successive inoculation. "Rabbits inoculated with a brain suspension of rabbit number fifty all died in seven days." This caused Pasteur to name the virus of number fifty "virus fixe," a virus of definite length. He now had obtained a virus of definite strength and the next question was, how could the virulence be gradually and definitely reduced.

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This he accomplished after many experiments. He proved that pieces of the "medulla oblongata" suspended in sterile tubes which contained fragments of caustic potash, steadily and gradually reduced their virulence as they dried, till the fourteenth day, when they were practically inert. New specimens were prepared each day and cords which had dried in one day Pasteur called "one-day virus;" cords which had dried in two days, "two day's virus," and so on up to the fourteenth day. With this graduated virus he now experimented on dogs, and the injection he used on the first day consisted of an emulsion of fourteen-day virus; for the second day, the thirteen-day virus, thus using a stronger virus each day, until on the fourteenth day he used the full strength virus. This treatment produced what is called immunity in the dog, and even the direct inoculation into the brain of the strong virus would not produce death.