# Tropical Diseases/Chapter 11

CHAPTER XI
L E I S H M A N I A S I S
UNDER the term " leishmaniasis " at least three diseases of man are included, viz. kala-azar, oriental sore, and espundia. These disease?, though clinically quite distinct and having each a definite topical and geographical distribution, are all associated with what optically appears to be the same organism, Leishmania. But though their respective organisms appear to be morphologically identical, it is by no means justifiable to conclude that they are specifically identical. The Leishmania form is common to many protozoa; it is merely a stage—— an immature stage—— and until the life-history is quite complete, and the natural history of the parasites of these diseases has been worked out, our judgment as to their identity or otherwise should be suspended. If it turn out to be the case that the germ causes of the various clinical forms of leishmaniasis are specifically identical, we shall have to conclude that the special pathogenic properties of these germs have been conferred on them during their extracorporeal life, especially by passage through particular animal intermediaries. Herein lies a wide field for future investigation.
I. KALA-AZAB
Synonyms.—— Tropical splenomegaly, black sickness, Sirkari disease, Sahib's disease, Burdwan fever, kaladunkh, dum-dum fever, ponos.
Definition.—— An infective disease characterized by chronicity, irregular fever, enlargement of the spleen and often of the liver, the presence in these and other organs of Leishmania donovani, emaciation, anæmia, leucopenia and relative increase of large mononuclear leucocytes, frequently a peculiar hyper-pigmentation of the skin, and a high mortality. ​History.—— The earliest description of this disease is by Clarke, who states, in the Assam Sanitary Report for 1882, that as far back as 1869 the attention of administrative officers in Assam had been directed to a peculiar disease called by the natives kala-azar, the ravages of which decimated, and in some instances almost depopulated, numerous districts in the Garo Hills. Notwithstanding its peculiar clinical features, its great fatality, its mode of spread along the lines of communication, the almost constant absence of malaria parasites from the blood, and the inefficacy of quinine treatment, until recently kala-azar was regarded by the majority of physicians as "a bad form of malaria."
In 1889 Giles, who had been appointed to investigate the etiology of kala-azar, denied its malarial nature, and stated that the disease was "neither more nor less than ankylostomiasis," because he found the ova of the hookworm in the fseces of practically all the cases he investigated. Giles's theory furnished a plausible explanation of the peculiar way in which kala-azar spread, and which could not be satisfactorily accounted for by the malaria theory. It was accepted by some, with the reservation, however, that he had under- estimated the malarial element. Dobson strongly opposed the ankylostoma theory. He stated that in 116 cases of kala-azar he had found the hookworm in 75 per cent., in 212 cases of other illness he had found it in 73.20 per cent., and in 146 healthy men he had found it in 67.12 per cent.
In 1896 Leonard Rogers and in 1898 Ronald Ross were appointed to re-investigate the disease. Both agreed as to its malarial nature; the former regarding it as a malignant type of malaria, the latter as malarial disease to which some form of secondary infection was superadded.
In 1903 Bentley endeavoured to prove that kala-azar was a malignant form of Mediterranean fever, a disease which he suggested was probably introduced into India at the time of the Mutiny by British troops from Malta, Gibraltar, and other Mediterranean ports.
Owing to the absence of malaria parasites in the ​cases of tropical splenomegaly I had studied in this country, the absence of tertian and quartan periodicity in the fever, and the uselessness of quinine in its treatment, I had come for some years to regard this disease as non-malarial and as one sui generis. In 1903, struck by certain features common to trypanosomiasis and kala-azar, I ventured to suggest in the third edition of this manual that the latter disease might be a trypanosoma disease.
A few months later, Leishman published a paper " On the Possibility of the Occurrence of Trypanosomiasis in India," wherein he stated that in 1900, at Netley Hospital, at the post-mortem of a soldier who had died of so-called dum-dum fever, he had discovered in smear preparations from the spleen-pulp a number of small round or oval bodies, two or three microns in diameter, which on being stained presented, besides the nucleus, a smaller rod-like chromatin mass, set perpendicularly or at a tangent to the circumference of the larger nuclear mass. At the time he was unable to explain the nature of these bodies; but in May, 1903, on coming across similar bodies in the blood of a rat which had died of nagana, and the blood of which during life contained numerous trypanosomes, he surmised that the bodies found in the soldier in 1900 represented degeneration forms of trypanosomes.
In July, 1903, Donovan stated that he had found similar bodies three months previously in smears of the spleen taken post-mortem from cases said to have died from chronic malaria. On June 17th he found identical bodies in splenic blood taken during life from a patient suffering from irregular fever and enlarged spleen, and whose peripheral blood showed no malaria parasites. Identical bodies had also been found by Marchand in January, 1903, in sections of the spleen, liver, and bone marrow from a patient who had taken part in the Pekin campaign and had suffered from a long-continued irregular fever, extreme enlargement of the spleen, and anæmia.
In December, 1903, having under treatment a patient from Darjeeling suffering from typical kala​azar, I had the opportunity of examining blood abstracted from his spleen on two occasions, and found it swarming with the peculiar bodies already described by Leishman, Donovan, and Marchand. I was able to show that these bodies were not endocorpuscular parasites, as suggested by Laveran and Mesnil, who had expressed the opinion that they belong to the genus Babesia.
Then followed observations by a number of investigators, and we learnt that kala-azar was a widely distributed, though hitherto unrecognized, disease. It was found in various parts of the eastern side of India, in China, Arabia, the Soudan, Tunis, Sicily, Italy, Algeria, Crete, Spain, Portugal, Greece and the Grecian Archipelago,* Malta, the Caucasus, Central and South America, and South Africa, etc. Besides those of Leishman and of Donovan, amongst the most important papers on the subject are those of Christophers, who showed that the parasite attacks the endothelial cells; of Leonard Rogers, who in cultivating the parasite obtained a characteristic flagellated form; of Dr. J. H. Wright, of Boston, U.S.A., who found parasites morphologically indistinguishable from those of kala-azar in the granulation cells of tropical sore; of James, who confirmed and extended Wright's observation; of Patton, who considers he has discovered the extracorporeal developmental forms of the parasite in a species of bed bug; of Nicolle and Comte on the occurrence of the same or a similar parasite in children and dogs in Tunis, and in kittens in Algiers; of Laveran on experimental Leishmania, and many others. †
Epidemiology.—— Our knowledge of the epidemiology of kala-azar is gathered mainly from the Assam epidemic, which began about 1870, when the disease ​appears to have been introduced from Rangpur. Rogers believes that it was possibly a continuation of a similar epidemic, known as " Burdwan fever," which had been raging in Lower Bengal. This importation theory is supported by the names of " Sirkari disease " and " Sahib's disease " given by the Garos, who state that it was unknown among them until after the English took over their country, The epidemic began almost simultaneously at Bengal Kutta and Karaibari, two places fifty miles apart but in direct communication with the Rangpur district. It advanced very slowly along the valley of the Brahmaputra, taking seven years to spread less than a hundred miles. Following the lines of intercourse, it attacked first the larger stations, and then spread to the smaller villages around. The introduction of the disease into a village was almost invariably traced to someone coming with the disease on him from an infected locality. Some isolated villages escaped in a remarkable manner. Whilst the disease spread up the valley, the invasion of new places was counterbalanced by its dying down in villages and districts which had previously suffered. Generally, it clung to a place for about six years, and then disappeared without any apparent change in the local conditions. A house appeared to retain the infection for many months; the natives considered that it could not be reoccupied with safety under one year. During the course of the epidemic kala-azar never extended far above the level of the Brahmaputra valley. The disease did not arise in the first instance in the interior of the Garo Hills district, as some authors affirmed, but appeared first at the foot of the hills, and then spread between them along the patches of low, flat, terai country.
On account of its deadliness, especially in the smaller villages, kala-azar as it swept onwards became a terror to the natives. Those suffering from the disease were turned out of the villages; sometimes they were made unconscious with drink, taken into the jungle, and burnt to death. Some villages cut off all communication with neighbouring ​villages for fear of infection; other villagers deserted their homes and even migrated to a different district.
Although the foregoing is the only recorded example of kala-azar as a widespread and active epidemic, it had been recognized that a disease clinically identical occurred sporadically in several places in India and elsewhere. These cases had often been regarded as a form of malarial cachexia, but the identity of the sporadic and epidemic disease has now been established by the detection of the Leishman or Leishman-Donovan body in both.
In 1904 leishmania were discovered in Tunis by Cathoire, and important studies by the Sergents, Nicolle, and many others have shown that the parasite occurs in many of the islands and countries in the Mediterranean basin; that there it is practically confined to young children—infantile kala-azar—
Fig. 56.—Kala-azar parasites from the spleen, stained.
Leishmania infantum; and, further, that whilst in India dogs are hardly ever affected, in the Mediterranean basin a large proportion of these animals are naturally the subjects of leishmaniasis.
Etiology.—The kala-azar parasite (Plate V.) has now been relegated to the genus Leishmania, Ross. We know two stages of this body, intracorporeal and extracorporeal. Possibly these represent respectively asexual and sexual forms; the former found in man and in some other vertebrates, the latter obtained in artificial culture media, and, it may be, in certain insects—flies, bugs, fleas, lice, mosquitoes.
Parasites of kala-azar and oriental sore.
Kala-Azar: 1, Free forms from the spleen; 2 and 3, in the endothelial cells: 4, in the liver. Oriental Sore: 5, In endothelial cell: 6, free forms.
Plate V.
The Leishman or Leishman-Donovan body, as it is generally called, is a small ovoid or roundish organism measuring from 2 to 4 μ in diameter. Stained according to Leishman's method, it shows two lilac-coloured chromatin masses, one larger than the other, enclosed in a cytoplasm having a faint bluish tint about the periphery. The larger chromatin mass is the nucleus, which may be oval and centrally placed (resting stage), or elongated and at the periphery (pre-division stage). The smaller chromatin mass is the micronucleus or blepharoplast; it is usually in the shape of a short rod, and is placed perpendicularly, or at a tangent to the nucleus. It stains more deeply than the latter. The parasites multiply by simple fission, the division of the body being always preceded by the elongation and division of the nucleus and blepharoplast. The plane of division is always longitudinal. Some forms, having attained a larger size, suggest a process of multiple fission; these are almost circular, and present, as a rule, six chromatin masses, three large and three small, the former being placed round the periphery.
The parasites, as they occur in man, are probably almost invariably intracellular. They grow and multiply within the host cell, causing it to enlarge, and then, after disintegration of the nucleus, to disrupt. The parasites so set free either enter other endothelial cells or are taken up by the white blood-corpuscles, in which they are sometimes found in the ​peripheral circulation. In smear preparations they are often free or in clusters of various numbers, sometimes arranged with great regularity like the merozoites in the segmenting quartan or tertian malaria parasites. Sometimes as many as 50, or 200, or even more parasites are found together embedded in a structureless matrix or stroma, probably the remains of the original host cell.
In cultures (Fig. 57) the parasites enlarge very rapidly. They retain at first their shape, the cytoplasm becoming granular, opaque, and vacuolated. Having attained a diameter of 7 to 9 $\mu$, they assume an
Fig. 57.—Kala-azar parasites in cultures. (After Leishman.)
elongated pyriform shape and become flagellated. The flagellum arises from the blepharoplast at the rounded end of the parasite, and projects at once clear of the body as in Euglena. There is no undulating membrane as in trypanosomes. These flagellated forms measure from 12 to 20 $\mu$ in length. They multiply by longitudinal fission; sometimes throwing off exceedingly fine linear forms (Leishman), comparable in their delicacy to spirochætes. They move actively with the flagellum in front, and towards the twelfth day tend to agglomerate in rosette groups, the flagella being directed centrally.
The culture medium used by Rogers was blood to which a small quantity of sterile, slightly acid citrate of soda solution was added to prevent ​lation. When the culture medium was kept at blood heat the parasites very rapidly degenerated and disappeared; but when placed in an incubator at 27° C. they lived for three or four days and multiplied. A lower temperature was found to be even more suitable. When temperature was lowered to 20°-22° C. the parasites multiplied more readily, acquired a considerable size, and finally assumed the elongated, motile, flagellated form. The N.N.N. culture medium (p. 158) gives excellent results, and in this, by transplanting at intervals of from twelve to fifteen days, the cultures can be kept alive up to at least four years. The presence of moulds does not affect the cultures, but bacterial contamination is fatal.
Animal experiments.—— The early attempts in India to communicate kala-azar to the lower animals failed, but Nicolle in Tunis, and, subsequently, many others elsewhere, have shown that dogs, cats, jackals, monkeys, rats, mice, and to a less extent guineapigs and rabbits, are inoculable, provided laige doses of the virus are injected into the liver or peritoneal cavity. For a dog, 2 to 4 c.c. of a thick emulsion of infected liver, spleen, or bone marrow in normal saline usually suffices. Intravenous injection is not so successful. Injection of cultures sometimes succeeds. Archibald succeeded, in Khartoum, in infecting a monkey by feeding it on kala-azar material.
Mode of transmission.—— This has not been definitely ascertained as regards India, but there is evidence that in the Mediterranean countries the dog* is a principal reservoir of the disease, and may be concerned with the endemicity. It has also been asserted, but not proved, that the dog-fleas, Pulex serraticeps and Ctenocepkalus canis, are the transmitters. So far as ascertained, wherever kala-azar occurs, there the dogs are infected with L. donovani in variable proportion from 1-8 per cent, to 81 per cent. In India Donovan has failed to find, except in a negligible proportion of instances, naturally ​infected dogs. Strange to say, although the dog has been found to be easily infected in the Mediterranean area, in India it seems to be partially immune and only contracts the disease after massive intraperitoneal injections of leishmania-infected organs.
The exact way in which the flea transmits the virus, if it be the transmitting agent, is not known whether the parasite undergoes important biological changes in the insect, or whether the latter functions merely in a passive or mechanical way.
Patton has put forward a claim for the bug as the transmitter of Indian kala-azar. It may be so, but conclusive proof has not been adduced. Should the conjecture be confirmed it would afford an explanation of the tendency of the disease to cling to particular localities and houses, and it would supply a valuable guide to prophylaxis.*
Under natural conditions kala-azar, like other diseases caused by similar protozoal organisms, is probably transmitted by a living agent. There are certain facts, however, which tend to suggest that the carrier need not necessarily be a blood-sucking animal. In the first place, the parasite in man is not, as a rule, in great abundance in the peripheral circulation. Secondly, the parasite is often present in ulcerations of the skin and of the intestinal mucosa,suggesting elimination by these organs. Mackie found leishmania-like bodies in the mucus of dysenteric cases of kala-azar. Thirdly, we know that although some species of Herpetomonas are fostered by blood-sucking flies, such as Tabanus and Hœmatopota, others are found in non-biting forms, such as Musca, Sarcophaga, Pollenia, and Fucellia, which could become infected only by settling on ulcerations or on fæcal matter. It is conceivable that such insects might transmit the infection of kala- azar by depositing the parasites on wounds and abraded surfaces. It has been suggested that there ​is a reservoir in some of the lower animals for leishmania, e.g. the house-lizard. The history of the Assam epidemic is against this view, for it has been definitely shown that the disease was introduced and spread by man, and that it did not pre-exist in the invaded districts, as would have been the case had there been an animal reservoir.
Predisposing causes.—— Kala-azar attacks both sexes and all ages, but, unlike malaria, it shows a predilection for the acclimatized the natives; in them it is said to be as severe and fatal as in the case of new-comers. In the Mediterranean basin it occurs almost though not quite exclusively in children (five months and upwards); in India it occurs at any age. The reason for this discrepancy as regards age has not been explained.
Incubation period.—— This is difficult to fix. In the case of one Englishman, recently under my care, the time that elapsed from his arrival in perfect health in the endemic region and the onset of the fever which terminated in kala-azar (diagnosed microscopically both before and after death) was under ten days. In a proportion of instances, as in some artificially infected dogs, and as is the case in dermal leishmaniasis, the disease may remain latent for months. In fatal cases in man the parasite may disappear from the tissues before death; what appears to be an explanation of this curious fact has lately been advanced by Archibald, who found certain coccoid bodies by hepatic puncture in these latent cases; he believes that these bodies represent a stage of the parasite.
Symptoms.—— Bentley, speaking from a large experience in Assam, and with full knowledge of the literature of epidemic kala-azar, says that the disease commences with high fever, which may be preceded by rigor and, in some cases, by vomiting. This initial fever—— intermittent in some instances, more frequently remittent—— may be very severe. It lasts for from two to six weeks, occasionally longer. During its progress the spleen and liver enlarge, increasing and decreasing at first, often in a most ​remarkable degree, in harmony with the fluctuations of the fever. Then comes a period of apyrexia and general improvement, to be followed once more by fever and splenic and hepatic enlargement, and perhaps tenderness. In this way spells of fever and apyrexia recur for months, absolutely unchecked by quinine, until finally a low form of fever, rarely over 102° F., becomes more or less persistent. Profuse sweats are common during remissions at all stages of the fever; rigor is rare. Pains in the limbs often suggest rheumatism. When the disease is thoroughly established emaciation and anaemia become noticeable, and, together with the enlargement of the liver and spleen, cause the patient to present a typical appearance. Œdema of the legs, sometimes circumscribed œdemas, or even ascites may now be present. In many the skin acquires an extraordinary earthy-grey colour; the hair is apt to become dull, dry, and brittle, and may fall out; petechiæ, in the axillæ especially, are not unusual; epistaxis and bleeding from the gums are common. This condition of chronic fever, enlargement of spleen and liver, emaciation and anæmia, may continue for months, or even one or two years, until improvement sets in, or more usually—— 96 per cent, of cases (Rogers), 150 recoveries in 2,000 cases (Price), 24 in 100 cases (Lignos)—— until the patient is cut off by intercurrent disease, especially dysentery (90 per cent.), occasionally phthisis, pneumonia, cancrum oris, or asthenia.
According to Rogers, the degree of anæmia, in uncomplicated cases, is usually only a moderate one, the number of red corpuscles being not infrequently over 4,000,000, and, as a rule, over 2,500,000 even in advanced cases. The most remarkable change in the blood is the great and constant reduction in the number of leucocytes. Instead of there being 1 white to about 625 red, as in a normal subject, the proportion is commonly from 1 to 2,000 to 1 to 4,000, and may be lower still. The reduction is most marked amongst the polynuclear variety; the lymphocytes and large mononuclear leucocytes, although greatly reduced in ​number, show a relatively increased percentage as in some other protozoal diseases. He further states that the alkalinity of the blood is diminished.
In those cases which I have had an opportunity of carefully watching I have been struck with the fact that, notwithstanding the chronic fever and progressive wasting, throughout the long illness the tongue has been almost uniformly clean and the appetite and digestion good.
Morbid anatomy.—— The spleen is greatly enlarged and the thickened capsule may show signs of perisplemtis. The trabeculse are enlarged, the pulp increased in bulk and full of blood. A section or smear preparation, appropriately stained, will show prodigious profusion of parasitic growth in the crowds of the large mononuclear cells already referred to. The liver also is generally much enlarged. It has a brown or mottled section. The parasites are in great abundance, occupying large mononuclear cells, attached or free, in the dilated hepatic and portal capillaries. There may be some cirrhotic changes, but the hepatic cells, though atrophied and perhaps fatty, never contain parasites. The bone marrow is similarly packed with parasite -lad en cells. Intestinal ulcerations is very common, and parasites may be found in the walls of the ulcers as well as in skin lacerations or in the lymphatic glands. Occasionally they are found in connection with the blood-vessels in the kidneys, but never in the epithelium of the secreting tubules.
Diagnosis.—— Irregular chronic fever with enlargement of the spleen and a relative mononuclear leucocytosis in patients from the endemic zone suggests kala-azar. An examination of the blood can at once exclude leucocythæmia and, if taken together with absence of tertian or quartan periodicity and the inefficacy of quinine, malaria. Trypanosomiasis and kala-azar may be difficult to distinguish between, and unless their respective parasites are detected a positive diagnosis is impossible, although geographical considerations and subsidiary skin and lymphatic lesions may assist in forming an opinion, ​Banti's disease and tropical splenomegaly clinically approach very closely, and can only be excluded by a microscopical examination of the liver and spleen juices, or of the blood. Similarly, malignant disease of the abdomen, so often associated with irregular chronic fever, in the absence of a satisfactory microscopical examination of liver or spleen juice, may be difficult to distinguish from kala-azar.
On the discovery of the germ cause of kala-azar, and the fact that this disease is widely distributed throughout the tropics and sub-tropics, there was at first a tendency to regard all cases of febrile tropical splenomegaly which are not associated with malaria, trypanosomiasis, and other well-known conditions, as kala-azar. Further observation and experience have considerably modified this view, since it has been found that a proportion of such cases do not show the Leishman body either during life or after death. Possibly other protozoal germs, as yet unrecognized, are responsible for some of these cases. So that, in any given case of tropical splenomegaly, until the Leishman body is found it would be rash to pronounce a positive diagnosis of kala-azar.
The discovery of the Leishman body in the blood,* lymph, or tissues, therefore, is the only reliable indication of kala-azar. In the first instance it should be sought for in the blood, or in material obtained by puncture of lymphatic glands, after appropriate staining. A high-power immersion lens is indispensable, and every leucocyte or scrap of tissue must be carefully scrutinized for the little oval body with the round or oval nucleus and rod-shaped blepharoplast. Several films, especially at the edges of the preparations, must be searched in this way before recourse is had to splenic or, better as being less dangerous, hepatic puncture.
Splenic puncture must not be lightly undertaken. A preliminary examination of the blood should always be made, not only with a view to ascertain ​the presence of the Leishman body, but to exclude leucocythæmia and obviate the necessity for splenic puncture, and the attendant risk of fatal hæmorrhage so easily induced in that disease. Death from hæmorrhage has frequently followed this seemingly trivial procedure. When the liver is enlarged, being a less vascular organ and less easily torn, it should be selected for punctures in preference to the spleen. The abdomen had better be fixed firmly with a binder to prevent as far as possible movement of the diaphragm and consequent risk of tearing the punctured organ. A fine hypodermic needle, scrupulously clean and dry,* and connected with the barrel of the syringe by a short length of rubber tubing, should be used, the patient being directed not to start or breathe while the puncture is being made. Failure to draw blood is not to be regarded as failure to obtain material for microscopical examination ; on the contrary, it is an advantage, as the object is to procure spleen or liver pulp, not blood. After blowing out the contents of the needle on a slip, a film should be spread and, after it has dried, stained by Irishman's or Giemsa's procedure, and then examined with a 1/12th objective. The parasite is easily recognized by its size, shape, and two chromatin masses.
Treatment.—— Until recently this, as a rule, was most unsatisfactory. Intercurrent malarial attacks may advantageously be treated with quinine, but for the disease itself this drug, even in huge doses and persisted with for long periods, is useless, if not harmful. Arsenic has proved equally unsatisfactory. Intravenous injections of salvarsan have been followed by favourable results. Splenectomy has been tried, but has failed. I have treated four cases with intramuscular injections of atoxyl. In two of these there was no improvement, the disease running its usual fatal course; but in the other two cases recovery ensued, whether as a result of the treatment or not I cannot assert. The arsenical is now quite superseded by the antimony treatment, introduced by ​Machado and Vianna in Brazil for dermal leishmaniasis, and subsequently applied to kala-azar by Castellani, Rogers, and others with remarkable success. If instituted before the case has become hopeless it seldom fails to ensure recovery. The drug may be given as in trypanosomiasis (see p. 180). The expulsion of intestinal parasites, change to a healthy climate, good food, warmth, rest, physical comfort, and good hygienic conditions are indicated.
Prophylaxis.—— Having regard to the character of the disease, in the endemic districts the cases should be dealt with as infectious; they should be isolated, and their houses and fomites should be disinfected or burnt. Domestic and personal cleanliness is of great importance. Infected dogs and cats should be destroyed ; and as far as possible, in the endemic districts, dogs should be kept free from fleas and not in too close association with man. By segregation of the sick, burning of houses, clothing, and furniture, etc., and provision of new huts, Price, Rogers, and Young have succeeded in exterminating the disease in infected coolie lines.
Oriental sore and kala-azar.—— If the parasite of oriental sore be specifically identical with that of kala-azar, it must somehow have been deprived of its virulence; for, although kala-azar is a fatal disease, oriental sore is eminently benign. It is known that one attack of oriental sore confers immunity against further attacks of the same disease. It affects dogs and other animals. May it not be that the virulence of the Leishman body is removed by passage through some animal other than man; or, possibly, by being transmitted by some intermediary other than that which transmits the virulent kala-azar? If this be so, we have at hand a vaccine against kala-azar. The idea is worth testing: " Are those who have had oriental sore immune as regards kala-azar, and vice versa?" * In support of this suggestion it has long ​been recognized in India that in districts where kala-azar is common oriental sore is rare. Recent work has shown that this is partially true for the Mediterranean area also. In Teheran the dogs are found infected with dermal leishmaniasis, and a general infection combined with cutaneous lesions has been produced in mice by intravenous injections of cultures of Leishmania tropica (the parasite of oriental sore), and sores in monkeys by cutaneous inoculation of cultures of Leishmania donovani.
II. ORIENTAL SORE
Synonyms.—— Tropical sore, bouton d'Orient, Delhi boil, etc.
Definition.—— A specific ulcerating granuloma of the skin, endemic within certain limited areas in many warm countries. It is caused by a species of Leishmania, and is characterized by an initial papule, which, after scaling and crusting over, generally breaks down into a slowly extending and very indolent ulcer. Healing after many months, it leaves a depressed scar. The sore is inoculable and, usually, protective against recurrence.
Geographical and seasonal distribution.—— Among the endemic places may be named Morocco, the Sahara (Biskra, Gafsa), the Niger, Egypt, Crete,Cyprus, Asia Minor, Syria (Aleppo), the Soudan, Mesopotamia (Bagdad), Arabia, Persia, the Caucasus, Turkestan, India (Lahore, Multan, Delhi, etc.). Juliano describes the disease as being common in Bahia, Brazil, and cases are reported from Bolivia, Peru, Panama, and French Guiana—— where it is called "pian bois," " bosch-yaws," etc. The name oriental sore, suggested by Tilbury Fox, is therefore no longer quite appropriate.
Locally, oriental sore is often called after some town or district in which it is specially prevalent; thus we have Delhi boil, Bagdad boil, "clou de Gafsa" and so forth. It is much more common in cities than in the country. In Bagdad few escape an attack; visitors of a few days only are almost certain, at particular times of the year, to contract it. ​According to Hirsch, in the tropics this form of ulceration is especially prevalent about the commencement of the cool season; in more temperate climates, towards the end of summer or beginning of autumn. Years of prevalence may be succeeded by years of comparative rarity; possibly in harmony with altered sanitary conditions. In Delhi, for example, in 1864 from 40 to 70 per cent, of the resident Europeans were affected with the local sore; on certain sanitary improvements being effected, the frequency of the disease was immediately materially reduced.
Histology; etiology.—— Section of the papule displays an infiltration of the derma by a mass of small round granulation cells. These lie between the elements of the tissues, particularly about blood-vessels, lymphatics, and sweat-glands; towards the centre of the lesion they completely replace the normal structures. Various micro-organisms have been described in association with oriental sore. By staining sections in gentian violet and afterwards partly decolorizing in spirit, Cunningham and Firth found certain violet-stained bodies (Helcosoma tropicum), varying in size and grouping, in a proportion of the infiltrating cells. These bodies Cunningham was inclined to regard as parasites. Riehl looked upon them as the result of a hyaline degeneration of protoplasm, and advanced a claim for certain micrococci which he said he found in great profusion in the granulation cells. That Cunningham's view is correct was proved by an American observer, H. Wright, who, in 1903, found in the granulation cells of an oriental sore the Leishman body (Cunningham's parasites) in gi-eat profusion. This observation has been abundantly confirmed in India and elsewhere; so that it may now be considered as definitely established that the cause of oriental sore is the Leishman body, or a body morphologically identical with this parasite. For the characters of the Leishman body, see p. 208 and Plate V.
The cultivation of the parasite, first carried out by Nicolle, is easily effected in the N.N.N. medium. ​The surface of a non-ulcerating sore is first painted with iodine and then punctured with a fine syringe. The parasites, as in the case of L. donovani, grow best in the ondensation water. Inoculation of cultures has given rise to lesions in monkeys.
In what way, under natural conditions, the parasite enters the tissues it is as yet impossible to state definitely. Not improbably it is conveyed by flies or other biting insects, and by them either inserted into the skin or applied to some pre-existing wound or sore. Dogs in Teheran, and perhaps camels, are subject to this or a similar disease. Monkeys and dogs have proved to be experimentally inoculable, while donkeys, horses, goats, and sheep are refractory. It must not be overlooked that in susceptible animals an important source of infection may lie.
Probably there are two methods of infection (a) direct, the Leishman body being directly inoculated without undergoing sexual or other developmental change; (b) indirect, in which an infected fly, bug, or other insect, either itself or through its progeny, conveys to the new host the parasite which in the meantime has undergone evolutionary changes.*Wenyon has proved that the parasite is unable to enter through the unbroken skin.
As a rule, second attacks do not occur. Observing this, the Jews of Bagdad at one time practised on their young children oriental-sore inoculation.
Neither race, nor sex, nor age, nor occupation, nor social condition materially influences susceptibility.
Incubation period and constitutional symptoms.—— The incubation period of oriental sore is variously stated in days, weeks, or months. That it may be a brief one, a few days or weeks, seems to be established by the appearance of the sore within a short time of arrival in endemic districts, or after ​inoculation. That it can be of much longer duration is equally certain. I have seen an unquestionable oriental sore which did not appear until five months after the patient had been exposed to any possibility
Fig. 58.—Oriental sore. (After Wenyon. From photo by R. McKay, reproduced in "Journ. Lond. School Trop. Med.")
of infection. Wenyon inoculated himself with oriental sore in Aleppo; it was not until six and a half months later that a leishmania-containing papule, subsequently developing into a sore, appeared at the site of inoculation. In other cases the incubation ​period has been as much as fifteen months, or even longer.
There is very little reliable information about the presence or absence of constitutional symptoms. It is customary to describe the disease as non- febrile. This may be true in most cases, but I am not convinced that it is so in every case. It is obvious that in a disease with, at least in some instances, a very prolonged incubation period, slight or even severe fever might be overlooked or misinterpreted. Oriental sore produces an immunity against itself. There must, therefore, be profound constitutional change. In other diseases attended with similar change fever is almost invariably present at one time or another in their course. In the case just alluded to as occurring in my experience, a severe anomalous fever, of five or six weeks' duration, preceded by eight months the appearance of the local lesions. In Wenyon's case the development of the initial papule was preceded by smart fever supposed at the time to be influenzal. Seeing, as has been pointed out (p. 218), the close connection of oriental sore with kala-azar, this question of the constitutional symptoms in the milder disease is an important one, and should be carefully studied.
Symptoms.—— The local lesion in oriental sore commences as a minute, itching papule which tends to expand somewhat as a shotty, congested infiltration of the derma. After a few days or weeks the surface of the papule becomes covered with fine, papery scales. At first these scales are dry and white; later they are moister, thicker, browner, and adherent. In this way a crust is formed, which on falling off, or on being scratched off, uncovers a shallow ulcer (Fig. 58). The sore now slowly extends, discharging a scanty ichorous material; this from time to time may become inspissated and a crust forms, while the sore continues to spread underneath. The ulcer extends by the erosion of its perpendicular, sharp-cut, and jagged edge, which is surrounded by an areola of congestion. Subsidiary sores may arise around the parent ulcer, into which they ultimately ​merge. These sores, usually about an inch in diameter, may come, in some instances, to occupy an area several inches across.
After a variable period, ranging from two or three to twelve or even more months, healing sets in. Granulation is slow and frequently interrupted. Often it commences at the centre whilst the ulcer may be still extending at the edge; often it is effected under a crust. Ultimately a depressed white or pinkish cicatrix is formed. Contraction of the scar may cause considerable and unsightly deformity.
Oriental sore may be single or multiple. Two' or three sores are not uncommon; in rare instances as many as forty have been counted on the same patient. They are mostly situated on uncovered parts hands, feet, arms, legs, and, especially in young children, on the face; rarely on the trunk; never on the palms, soles, or hairy scalp. Seidelin, Darling, and Connor have described as occurring in South America oriental sores with a predilection for the margins of the ears.
Dr. Sturrock, who practised in Bagdad for four years, informs me that in rare instances the disease recurs more than once, but, as a rule, the sores of the second attack do not break down. He has also seen a chronic type of the disease, which may recur and persist for several years and be associated with deposit in the testes, in mucous membranes, as well as with a chronic form of dactylitis.
In a very few instances the initial papule does not proceed to ulceration, but persists as a scaling or scabbing, non-ulcerating, flattened plaque just as sometimes happens in the case of the primary sore of syphilis. Sometimes the ulcer is quite superficial, an erosion rather than an ulcer. Occasionally, from contamination with the virus of some other infectious acute inflammatory skin disease, the primary lesion may become complicated, and perhaps a source of serious danger. Otherwise, oriental sore is troublesome and unsightly rather than painful or dangerous.
According to Nattan-Larrier there is a mononuclear leucocytosis in this form of leishmaniasis similar to that in kala-azar. ​Treatment.—— Some have advocated destruction of the primary papule, and even of the ulcer, by caustics or by the actual cautery; but a knowledge of the nature and natural progress of the disease suggests a protective and soothing rather than an irritating line of treatment. A dressing with some mild antiseptic ointment, as of iodoform, boric or salicylic acid, is indicated. Favourable results are reported from the application of an ointment consisting of equal parts of lanoline, vaseline, and methylene blue. Recently Row seems to have had prompt cures from hypodermic injections of killed cultures of the Leishmania parasite. The dose of a rich culture on N.N.N.medium, to which 5 drops of glycerine had been added forty minutes before, was ⅜ c.c. This may be repeated a few days later. Dr. Andrew Duncan informed me that in India he had seen these sores treated with great success by bandaging over them a piece of thin sheet-lead. Most probably these were not true oriental sores, which, as analogy would lead us to think, could heal only as the result of a specific treatment or on the establishment of immunity. X-ray and light treatment have been tried, with success in some cases, and unfavourable results in others. The reports on radium, salvarsan, and CO 2 snow treatment are decidedly favourable. These methods of treatment have been successfully superseded by antimony, given as in trypanosomiasis and kala-azar (p. 180). Tonics when the patient is anæmic or debilitated, attention to the general health, change of climate should the disease persist beyond the usual time, are indicated.
III. LEISHMANIASIS AMERICANA
Under the terms espundia, bubas braziliana, uta, pian bois, etc., several writers Carini, Paranhos, Splendore, Escomel, and others have described a very grave form of leishmaniasis occurring in certain South American countries *—— Brazil, Bolivia, Peru, ​Guiana, Martinique, Paraguay. Christopherson describes a case of the espundia type which he met with in the Soudan. In Paraguay it has assumed epidemic characters, and a large proportion of the population in certain districts is said to be affected.
Fig. 59.—Ulceration of hard palate and nares in leishmaniasis Americana. (After Splendore.)
The disease begins as a sore on some cutaneous or mucous surface (Fig. 59). The sore is of the chancrous form of the ordinary oriental-sore type. It heals in time, leaving a characteristic scar. After an interval of months or years, fungating and eroding ulcers (Fig. 60) of a most intractable character break out on the tongue, and on the buccal and nasal cavities, destroying and obstructing them, and ultimately, if untreated by antimony, after years of suffering, leading to the death of the patient by ​exhaustion. The lymphatic glands are often involved, but the abdominal and thoracic organs are spared.
Leishman bodies are to be found, though not in great profusion, in scrapings and sections of the fungating ulcers; giant cells also occur. Dermal ulcers of oriental-
Fig. 60.—Ulceration of nares and lips in leishmaniasis Americana. (After Splendore.)
sore type may concur with the buccal and nasal lesions. It is believed that the original sore in this grave form of leishmaniasis develops at the site of the bite of a jungle insect of unknown species. Treatment is the same as for oriental sore (p. 225).
Note.—The student is referred to Laveran's recently published work, "Leishmanioses" (Masson et Cie.), for a full and accurate discussion of this important subject.
* ↑ * In the Ionian Islands and Greece the disease known as " ponos" was found by Gabbi to be infantile kala-azar.
* ↑ † Nicolle gave the name Leishmania infantum to this variety of the parasite in order to call attention to the special liability of children to the infection in Mediterranean countries, and not because he considered it specifically distinct from the Indian form, which attacks adults and children indifferently.
* ↑ When existing in the blood in small numbers their presence can, in the hands of experts, be demonstrated by the N.N.N. cultural method. Centrifugation of the blood is of little use.
* ↑ * In the naturally infected dog, symptoms resembling rabies have been noted, by Nicolle, associated with the presence of leishmania in the spinal cord.
* ↑ * The discovery of a flagellated organism or of developing leishmania in the gut of an insect must not be regarded as adequate proof that the insect is the normal, or even a transmitter of the organism concerned.
* ↑ * Patton found the parasite in the blood in the first blood-film examined in 42 out of 84 cases, and in the remaining 42 after more or less prolonged examination of from two to twenty slides.
* ↑ * The presence of water in the needle will distort or burst the parasite and render it unrecognizable.
* ↑ * Nicolle has succeeded in producing a certain amount of immunity in dogs and monkeys to oriental sore and to kala-azar by injecting them intraperitoneally with cultures and infected material containing the leishmania of the local and of the general disease.
* ↑ * Patton has definitely stated that the bed-bug, Cimex rotundatus, is the transmitter of the disease in Cambay, India; these results Wenyou has failed to confirm. It is a mistake to conclude, because a parasite is capable of living for a time and even developing in the alimentary canal of some blood -sucking insect, that that insect is the natural transmitter of the disease. Wenyon has found developing leishmania from oriental sores in the stomach of mosquitoes.
* ↑ * La Cava has reported a similar disease affecting the nose and mucous membrane of the mouth, in Italy, in localities where oriental sore is also found.