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The incidence of kala-azar (visceral leishmaniasis) in the Maltese Islands is reviewed over 25 years (1948–1971). Features of the illness such as the almost exclusive occurrence in early childhood and the changes in plasma immunoglobulin patterns are discussed in relation to the known mechanisms of humoral and cellular immunity.

Epidemiological, clinical and laboratory data are reported on the outbreak of human visceral leishmaniasis in Emilia-Romagna in 1971–1972 which affected 60 individuals (42 adults and 18 children) with 13 deaths. A serological mass screening of 2,485 people in the area revealed the occurrence of 91 serum positive cases. Liver biopsy was carried out in 6 of these cases and revealed a peculiar form of granulomatous hepatitis which in 1 was accompanied by the presence of Leishmaniae. Some hypotheses are suggested on the possible causes of this outbreak.

The subgenus Larroussius of Phlebotomus includes several vectors of visceral leishmaniasis. A key is given for the tropical African species, three of which are described for the first time. Notes on the species include a discussion of the status of P. langeroni orientalis Parrot, one of the three species from the Ethiopian Region known to transmit leishmaniasis.

Summary A case of visceral leishmaniasis of exogenous origin was observed at the U. S. Marine Hospital, Baltimore, Maryland. The diagnosis was definitely established by sternal biopsy. A rapid response to treatment with ethylstibamine occurred, and the patient remained well during 2 months further observation. This patient showed a response to specific therapy which was somewhat more rapid than that usually seen. More prolonged observation following treatment would have been desirable but was not feasible in this case. In the experience of Most and Lavietes (4), while the average interval to relapse following Neostibosan treatment was 5.8 weeks, they found instances of late relapse, and advise observation for 4 to 6 months after treatment. They recommend Neostibosan as the drug of choice in the treatment of the initial infection. In this case the complement fixation test with L. donovani was positive before treatment. During convalescence, intradermal tests with L. tropica, L. donovani, and L. braziliensis were positive. While the interpretation to be placed on these tests is essentially unknown, the positive reactions are suggestive, and the tests may prove to be of value in investigation of suspected cases of leishmaniasis.

The sandflies of the two largest Italian foci of visceral leishmaniasis, Naples and Catania, were studied.The following species were found : P. papatasii, P. perniciosus, P. sergenti, P. vesuvianus, sp. n., P. parroti var. italicus var. n.P. papatasii and P. perniciosus are the commonest sandflies in the areas examined.Out of 1,547 ♀♀ dissected none showed a natural infection with Leishmania.P. papatasii was infected with Italian strains of L. infantum by feeding on cultures through membranes. The infection rate was low, but in contrast to Indian strains of L. donovani in the same sandfly, the infection once established did not die out.

It has been confirmed in this investigation that, in the cotton rat, L. donovani gives rise to infections of a progressive character with no tendency to spontaneous cure. In spite of the invasive powers of the parasite for the tissues of this host and the intensity of the resultant infections, the disease is of a relatively benign character. The normal architecture of the heavily infected spleen is not irreversibly changed as shown by the results of drug treatment which reduced the parasite numbers to submicroscopic levels. The absence of cytological changes in invaded liver epithelium is noteworthy. Bone marrow also maintained its functions as shown by absence of any significant change in the blood picture, and there was no evidence of change in the protein content of blood serum. Comparison of the growth rate of infected and non-infected animals over a period of 30 weeks indicated that the general health of the former remained unimpaired. The nature of the infection in the cotton rat as a whole appears to resemble that in the Chinese hamster (Cricetulus griseus) as described by Smyly and Young, 1924a , Smyly et al., 1924b and contrasts with the marked pathological character of the infection in the golden hamster. The parasitization of the parenchymatous cells of the liver of the Chinese hamster in advanced infections as noted by Meleney (1925) led, however, to degeneration of that organ and lesions were also present in the kidney.

Visceral leishmaniasis (Kala-Azar) has been reported with increasing frequency in the United States during the past two years. Search of the literature reveals the appearance of some thirty odd exogenous cases from various sources (1, 2, 3, 4, 5). Doubtless still other cases have been diagnosed and are as yet unpublished. Previous papers have adequately discussed the etiology, epidemiology, pathology, clinical and laboratory findings, and treatment of this disease (1, 2, 6, 7, 8). This report presents a case exhibiting the longest recorded interval between presumptive cure and relapse, two years having passed since “cure” was established and the first appearance of symptoms suggesting recurrence of activity. REPORT OF CASE R. G., a 32 year old white male, was admitted to the Veterans Administration Hospital, Washington, D. C., on November 2, 1947, complaining of intermittent fever of about four months duration with recent onset of general malaise and chills accompanying the fever.

1. (1) Seventeen species of sandflies are recorded from the Kitui District of Kenya, of which six are new ones. The new species are described. Observations are made on distribution, monthly incidence and bionomics. 2. (2) Eight species are known to bite man ;. these are P. martini, P. vansomerenae, P. schwetzi, P. kirki, P. garnhami, P. rosannae, P. harveyi, and P. multidens. P. garnhami is the only species caught biting in large numbers ; it has peaks of activity in the morning and evening. Sandflies have usually been caught biting near termitaries, sometimes in millet fields, and occasionally in houses. 3. (3) P. garnhami was at first considered the most likely vector of leishmaniasis north of Kitui, and flagellates undergoing “ anterior development ” were found in 5 per cent. of specimens fed on a cutaneous lesion containing abundant Leishmania. This infection rate is rather low for a potential vector, and now P. martini and P. vansomerenae are under suspicion. 4. (4) Many of the sandflies round Kitui like feeding on lizards. Flagellates (probably derived from lizards) have been observed in P. clydei, P. bedfordi, P. schwetzi, P. squamipleuris and P. garnhami.

Summary In Paloich District of Upper Nile Province, Sudan, an area with a long history of heavy kalaazar endemicity, no Leishmania infection was found in Phlebotomus papatasi and laboratory experiments suggest that this sandfly species is an inefficient vector of strains of L. donovani from man in this Province. Pure pools of P. orientalis (average 6 or 7 flies per pool) from small villages showed a remarkably high infection rate—30 positives in 180 pools examined (16.7%). In forested areas within a mile of these villages, 35 of 347 (10.1%) P. orientalis pools were infected. (Individual dissection of 1,150 P. orientalis by Donald Heyneman6 revealed a comparable rate of infection and heavy, anterior concentrations of leptomonads, indicating the efficiency of this sandfly as a vector.) Of the hamsters into which infected sandfly pools were inoculated, 54% developed a visceral leishmaniasis clinically and pathologically identical to that produced by Leishmania donovani in these animals. Since all sandflies were collected while biting humans in an area of heavy kalaazar endemicity, this organism is probably L. donovani. Four Nile Grass Rats, Arvicanthis niloticus luctuosus Dollman, were also found naturally infected with visceral leishmaniasis in forest sites in which numerous infected P. orientalis were taken. No man-biting sandflies were found in grasslands, or in forests within a mile of the Nile. P. orientalis was widely distributed inland in Acacia and Acacia-Balanites forests, as well as in small and larger villages in forest clearings and close to forests. In villages away from forests, P. orientalis was less common or absent. Leishmania infections were found in P. orientalis wherever this sandfly occurred. P. papatasi was present in established villages and was sometimes a serious pest. Except in a single locality about 200 yards from a village where small numbers of P. papatasi were taken, this species was extremely rare or absent in forested areas.

Attempts to transmit kala-azar to five human beings suffering from advanced malignant disease by massive injections of cultures of L. donovani in all the cases and additional injections of leishmania from the livers and spleens of infected Syrian hamsters in two cases were negative in four cases during an observation period of from 8 to 17 months. In one case (Case 3) of cylindrical-celled carcinoma of the stomach, the patient became infected after inoculation of cultures of L. donovani. This is the first record of the successful transmission of visceral leishmaniasis in man. The incubation period was less than 5 months. This case was observed for a period of 9 months and during all this time showed no signs or symptoms of kala-azar in spite of a very heavy infection. There was no marked enlargement of the spleen, no fever and no leucopenia. The histological and haematological findings are discussed. The serum of the infected case was lytic for his own strain of L. donovani. The action of normal human serum or flagellates of Leishmania consists of damage to the nuclear wall and the pouring of the nuclear contents into the protoplasm. Two types of cell infection were noted, one in which the protoplasm is packed with parasites as in the case of reticular cells of the spleen and Kupffer cells in the liver, and one in which the cell is relatively slightly parasitized as in the adventitial cells of arteries, trabeculae Of the spleen, Glisson's capsule, the connective tissue forming the stroma of a carcinoma. The infection of the reticular cells of the bone marrow was intermediate between these two types. In spite of their infection Kupffer cells and other infected cells remained actively phagocytic as evidenced by the inclusion in them of plasma cells, lymphocytes and even other infected cells. Connective tissue cells in the stroma of a cylindrical-celled carcinoma and in Glisson's capsule are shown to be potential phagocytes. The factors which determine individual susceptibility to kala-zar are quite unknown.

(1940). The Use of Certain Aromatic Diamidines in the Treatment of Kala-Azar. Annals of Tropical Medicine & Parasitology: Vol. 34, No. 3-4, pp. 181-197.

A new focus of human and canine kala-azar in Hangchow and surroundings is described. The probable cause of its presence is the mass migration of human beings due to the war.

Many children present themselves with the dysenteric, typhoidal and pneumonic types apart from the usual afebrile and febrile types which are the classical forms of the disease. Smears from the nasal mucus reveal Leishman Donovan bodies. The practical difficulties encountered on the therapeutic side are the time for cessation of treatment, the necessary attention to resistant and relapsing patients and the frequent development of hepatic cirrhosis.

1. (1) Certain features of the epidemiology of Sudan kala-azar suggest that the infection may be maintained by some alternative or reservoir host in the absence of man. 2. (2) Casual leishmania infection has been found in a horse, a monkey, and possibly in a fox, but no animal reservoir has been identified although many animals have been examined. 3. (3) Canine leishmaniasis has not been found in the Sudan but, in my opinion, its absence has not yet been established.More work is required in the Tapotha area. 4. (4) Subjects of post kala-azar dermal leishmaniasis may provide a human reservoir of infection, but this is unlikely to be the complete explanation of leishmaniasis in the Sudan.

(1969). Mucosal leishmaniasis in the Sudan. Annals of Tropical Medicine & Parasitology: Vol. 63, No. 1, pp. 123-128.

Although it is now more than twenty years since Sergent (1905) suggested the possibility ofPhlebotomusbeing responsible for the transmission of Oriental Sore, it was not until 1921 that any direct evidence was produced in support of this hypothesis. In that year Sergent, Parrott, Donatien and Beguet (1921) collected a large number ofP. papatasiifrom a neighbourhood infected with Oriental Sore and inoculated their contents into human subjects ; subsequently, the characteristic lesions developed at the sites of inoculation, from which typicalLeishmaniawere recovered. Similarly, Aragao (1922) produced in a dog a cutaneous nodule containingLeishmania, by inoculating crushed sandflies (P. intermedius) that had been fed on a case of Brazilian Leishmaniasis 13 days previously. The first demonstration of the development ofLeishmaniain the sandfly, however, was furnished by Knowles, Napier and Smith (1924), who found flagellates in the gut ofPhlebotomus argentipesfed on Kala Azar patients in Calcutta. This discovery has been confirmed and extended by the subsequent investigations of the Indian Kala Azar Commission. Christophers, Shortt and Barraud (1925, A and B), working in Assam, also found thatL. donovanideveloped in the midgut ofP. argentipesfed on suitable cases ; the infection was especially well developed on the fifth day, the flagellates being found attached to the wall of the gut up to the hinder end of the pharynx. Finally, Shortt, Barraud and Craighead (1926) carried the development a stage further by demonstrating the presence of flagellates in the buccal cavity, in close proximity to the commencement of the biting parts. These results, combined with the careful epidemiological investigations recorded in Report No. 1 of the Indian Kala Azar Commission (1926), would seem to justify the view held by this Commission that the sandfly is probably the vector of the parasite of Kala Azar. Moreover, the recent observations of Adler and Theodor (1926), who succeeded in producing infection with Oriental Sore by the inoculation of flagellates from the alimentary canal ofP. papatasiipreviously fed on an infected case, shows that in this closely related species ofLeishmania, the sandfly is certainly capable of harbouring the organism in an infective form.

Summary 1. Following a single intramuscular injection of pentavalent antimonials, there was a progressive decrease in the number of viable L. donovani in the spleen of infected hamsters, the decrease continuing as long as 16 to 32 days after injection. 2. Possible explanations for this prolonged action, and its implications for the treatment of leishmaniasis in man, have been discussed.

O autor descreve dois novos casos de leishmaníose visceral em Pernambuco, Brasil e observados no Instituto de Medicina Tropical da F.M.U.F.Pe. O primeiro faleceu antes de receber o tratamento específico e o segundo curou-se após uma série de tratamento com o antimoniato de N-metil-glucamina.

1. 1. Leishmania parasites have been found in the skin of kala-azar patients in the Anglo-Egyptian Sudan. 2. 2. The frequency, type and distribution of the cutaneous lesions in which parasites have been found are described. 3. 3. It is suggested that these skin conditions are due to the parasites of kala-azar, and not to concurrent infection with the parasites of oriental sore. 4. 4. Leishmania have been found in the “juice” obtained by puncture of the inguinal lymph glands in thirty consecutive cases of kala-azar. 5. 5. The technique used in gland puncture is described, and its possible value in the diagnosis of kala-azar is discussed.

(1927). The Behaviour of Cultures of Leishmania sp. in Phlebotomus Papatasii. Annals of Tropical Medicine & Parasitology: Vol. 21, No. 2, pp. 111-134.

Summary 1. A case of accidental infection caused by Leishmania donovani is presented. It is believed to be the only reported case of leishmaniasis due to Leishmania donovani originating in the United States and the only reported case of an accidental infection in a laboratory worker due to this parasite. 2. The disease was manifest by swelling of a finger and regional epitrochlear and axillary adenopathy. There was no evidence of systemic infection. 3. The diagnosis was made by detection of the parasite in fluid secured by aspiration biopsy; in impression smears of the excised lymph node and fixed tissue sections of the lymph node, and growth in culture of the tissue on NNN medium. 4. The patient responded satisfactorily to treatment with Stibanose, a pentavalent antimony preparation. He has been followed for one year and shows no evidence of relapse.

La incidencia real de la leishmaniasis visceral (LV) y cutánea (LC) por Leishmania infantum en España no es bien conocida. Desde el año 2009 se desarrolla un brote epidémico en el sudoeste de la Comunidad de Madrid. Se realizó un estudio retrospectivo de los casos diagnosticados de LV y LC en otra área sanitaria del este de la Comunidad de Madrid, durante el periodo 1987-2016. Se revisaron los registros Salud Pública y del centro sanitario de referencia, el Hospital Universitario Príncipe de Asturias de Alcalá de Henares. En 30 años se registraron 69 casos diagnosticados de leishmaniasis, 43 viscerales (62,3%) y 26 cutáneas (37,7%), una de ellas mucocutánea. La tasa de incidencia global anual se ha mantenido estable oscilando entre 0 y 1,90 casos por 100.000 habitantes. Los casos de LV y coinfección con VIH han ido disminuyendo gracias a los tratamientos antirretrovirales de gran actividad pero han aumentado los de pacientes con otros tipos de inmunodepresión. La incidencia de LC es similar a la de LV en los últimos 15 años aunque más irregular. Se notificaron a Salud Pública el 35,7% % de las LV y el 5,5% de LC por lo que se debe reforzar el sistema de notificación de leishmaniasis de cara a su control y detección de aumentos de incidencia. A nivel de otros países europeos endémicos, la incidencia de LV ha permanecido estable en España hasta el brote del año 2009, en Italia está disminuyendo después de otro brote epidémico y en Francia se mantiene estable., The actual incidence of visceral leishmaniasis (VL) and cutaneous (CL) by Leishmania infantum in Spain is not well known. Since 2009, an epidemic outbreak has been developing in the southwest of the Community of Madrid. A retrospective study of the diagnosed cases of LV and LC was carried out in another health area of the eastern region of Madrid during the period 1987-2016. Reference hospital, University Hospital Prince of Asturias of Alcalá de Henares and Public Health records were reviewed. In these 30 years, 69 cases of leishmaniasis were diagnosed, 43 visceral (62.3%) and 26 cutaneous (37.7%), one of them mucocutaneous. The annual global incidence rate has remained stable ranging from 0 to 1.90 cases per 100,000 inhabitants. Number of cases with VL and HIV coinfection has been decreasing due to highly active antiretroviral treatments but patients with other types of immunosuppression have increased. The incidence of LC was more irregular but similar to VL in the last 15 years. Only 35.7% of VL and 5.5% of CL were reported to Public Health, so the leishmaniasis notification system should be strengthened in order to control and detect incidence increases. At the level of European endemic countries, the incidence of VL has remained stable in Spain until the outbreak of the year 2009, in Italy it is declining after another epidemic outbreak and in France remains stable.

Summary1. Human red cells and serum are unfavorable to the growth of Leishmania donovani.2. A method is given for removing the red cells and serum from blood before planting.3. By this method blood cultures have been obtained from nine out of ten samples of blood from five patients, some of them after considerable antimony treatment.4. A modified “N.N.N.” medium is suggested.5. On this medium the Leishman-Donovan bodies from spleen punctures or peripheral blood develop into flagellates at all hydrogen-ion concentrations tested, i.e., between PH 6.8 and PH 8.2 and the flagellates grow at least to PH 9.0.6. Cultures on this modified medium show post-flagellate forms and perhaps Cornwall's “thick tails.”