Synonyms: Piroplasma donovani, Leishmania infantum, L. canis, L. chagasi.
Disease: Kala-azar; dum-dum fever; visceral leishmaniosis.
Hosts: Man and the dog are the principal hosts of L. donovani. Infections have also been reported in the cat by Sergent et al. (1912) and Bosselut (1948), in the sheep by De Paolis (1935) and in the horse by Richardson (1926).
Location: L. donovani occurs in the cells of the reticuloendothelial system, including both the endothelial cells and the circulating monocytes and polymorphonuclear leucocytes. The parasites are found thruout the body, but particularly in the endothelial cells of the blood and lymph vessels of the spleen, liver, bone marrow, lungs, kidneys, mesenteric lymph nodes and skin.
Types of Disease, Geographic Distribution and Epidemiology:
Five types of visceral leishmaniosis can be recognized:
1. Indian kala-azar or dum-dum fever is the classical type of the disease. It is found in India and affects young adults (60%) and children 5 to 15 years old. It does not occur naturally in dogs altho they can be infected experimentally. It is transmitted by Phlebotomus argentipes.
2. Sudanese kala-azar is found in the Sudan and Abyssinia. It affects people of the same ages as Indian kala-azar and does not occur naturally in dogs. It was found once in a horse (Kirk, 1956). Oral lesions are frequently present, and this type of the disease is relatively refractory to treatment with antimony compounds. It is transmitted by P. orientalis. A similar form occurs in small, isolated pockets scattered thru Africa south of the Sahara. It may cause skin lesions in addition to the visceral ones. It is a zoonosis, and has been found in a gerbil (Tatera vicina) and a ground squirrel (Xerus rutilus)( Manson-Bahr, 1959).
3. Chinese kala-azar is found in northern China. It is more common in children than in adults, and also occurs commonly in dogs. It is transmitted by P. chinensis and P. sergenii.
4. Mediterranean or infantile kala-azar is found in countries of the Mediterranean basin including southern Europe and in parts of tropical Africa. Dogs are much more commonly infected than man, and 90% of the affected people are children less than 5 years old. The incidence in dogs may reach 20% in some countries, and infection rates as high as 40% have been reported in Greece and Samarkand. Even in such countries, the infection rate in children is only 1 to 2%. Mediterranean kala-azar is transmitted principally by P. perniciosus and P. major.
5. South American kala-azar is found from Mexico to northern Argentina. It attacks human beings of all ages and also occurs in dogs and cats. In a monographic review of visceral leishmaniosis in Brazil, Da Silva (1957) stated that it is endemic and at times epidemic in certain areas, that it is transmitted by Phlebotomus longipalpis from a natural reservoir host such as the dog, and that it occurs mostly among persons with a low economic status and particularly among the children of that group. According to Deane (1956, 1958), the dog is the principal urban reservoir and the most important source of human infection, while the "bush-dog" (Lycalopex vetulus) is probably the principal rural one. The disease is also transmitted by P. intermedius.
Two cases of visceral leishmaniosis have been reported in dogs in the United States, one in Alabama by Thorson et al. (1955) and the other in Washington, D. C. by Gleiser, Thiel and Cashell (1957). Both dogs had been imported into this country from Greece.
Of the five types of visceral leishmaniosis, the Mediterranean, Chinese and South American are zoonoses while the Indian and Sudanese are not. The reasons for this are not clear, since dogs can be infected experimentally with the Indian and Sudanese denies of L. donovani. Adler and Theodor suggested that it may be because the Mediterranean type is transmitted by sandfly bites whereas the Indian type is transmitted when the sandfly is crushed on the skin. Since dogs and infants are not good flyslappers, they are not so likely to get Indian kala-azar.
Pathogenesis: Kala-azar is an important and highly fatal disease of man, particularly in India. After an incubation period of several months, it starts with an irregular fever lasting weeks to months. The spleen and liver hypertrophy. In advanced cases, there is ulceration of the digestive tract (mouth, nose, large intestine) resulting in diarrhea, and ulceration of the skin. There is great emaciation, but the abdomen is swollen. In untreated cases, the mortality is 75 to 95%, being a little higher in adults than in infants. Death occurs in a few weeks to several years, often resulting from intercurrent disease. In treated cases, 85 to 95% recover. Following recovery, whitish spots which develop into lentil-sized nodules may appear in the skin, particularly of the face and neck. This condition is known as post-kala-azar dermal leishmanoid.
Mediterranean kala-azar in children is similar to the above, but the disease usually runs a shorter course.
Kala-azar is essentially a reticuloendotheliosis. The reticuloendothelial cells are increased in number and invaded by the parasites. The cut surface of the enormously enlarged spleen is congested, purple or brown, with prominent Malpighian corpuscles. The liver is enlarged and there is fatty infiltration of the Kupffer cells. The macrophages, myelocytes and neutrophiles of the bone marrow are filled with parasites. The lymph nodes are usually enlarged and the intestinal submucosa is infiltrated with macrophages filled with parasites; these are especially numerous around the Peyer's patches. Intestinal ulceration, if present, is usually a secondary condition. There is progressive leucopenia accompanied by monocytosis. There may be anemia due to blockage of the reticuloendothelial system.
In dogs and also in the Brazilian bush-dog, L. donovani may cause either visceral or cutaneous lesions, but the latter are much more common. The disease is usually chronic with low mortality, altho an acute, highly fatal type is known. There may be emaciation and anemia. There is an abundant scurfy desquamation of the skin, and in some dogs more or less numerous cutaneous ulcers. In Chinese kala-azar, cutaneous lesions occur especially around the nose and ears. The hair is shed on parts of the body, particularly the head. The parasites occur in the macrophages in the subcutaneous tissues or in nodular lesions in the skin. They have also been recovered from healthy appearing skin. The visceral type of the disease is similar to that in man.
Diagnosis: The only sure diagnostic method is the demonstration of the parasites themselves, altho serologic and other tests have also been used and are of suggestive value. Smears made from biopsy samples of spleen pulp, liver pulp, superficial lymph nodes, bone marrow or thick blood smears can be stained with Giemsa's stain and examined microscopically. In visceral leishmaniosis, the spleen is most often positive, but a certain amount of danger is associated with puncturing a soft, engorged, enlarged spleen. Thick blood smears are more often positive in man than in dogs.
Examination of bone marrow obtained by sternal puncture is becoming increasingly popular. In the cutaneous form of the disease, scrapings should be made for staining from the lesions or from the dermis with as little bleeding as possible. This is probably the method of choice for dogs, since the cutaneous disease is more common than the visceral form in them. L. donovani can often be found in apparently normal skin in dogs and also, in the Sudanese and Middle Asiatic forms of the disease, in man (Manson-Bahr, 1959). Examination of the superficial lymph nodes is also valuable.
Leishmania can be cultivated readily in NNN medium or a similar medium. The medium is inoculated with spleen, lymph node or liver juice, bone marrow, blood, or excised dermis and incubated for a week to a month at 22 to 24° C. Leptomonad forms are present in culture. Leishmania can also be grown in chicken embryos (Trincao, 1948) and in tissue culture (Hawking, 1948); see Pipkin (1960) for a review of this subject.
Animal inoculation can also be practiced, but is not usually done because it takes several months. The golden hamster is the most susceptible laboratory animal.
The complement fixation test has been used with some success, particularly in man. It is often positive before the parasites themselves can be found.
The formol gel test (Napier's aldehyde test) is positive in more advanced cases. It is carried out by adding a drop of commercial formalin to 1 ml of serum. In a positive reaction the serum turns into a milky white gel; a clear gel is not positive. Organic antimony compounds, resorcinol, and many other compounds will also produce this reaction. It is due to an increase in euglobulin and decrease in albumin in the serum. It also occurs in diseases other than kala-azar.
Treatment: Leishmanial infections can be treated successfully with various organic antimony compounds. The cheapest is tartar emetic, which is administered intravenously. In man, at least 25 or 30 doses totaling at least 2.5 g must be administered daily or on alternate days. Pentavalent antimony compounds are more expensive, but they are less toxic, act more quickly, and most of them can be injected intramuscularly as well as intravenously. Even so, 10 or 12 doses totaling 2.7 to 4.0 g are needed. Among these compounds are neostibosan, neostam, solustibosan and urea stibamine. The aromatic diamidines, pentamidine and stilbamidine, have been used in treating human leishmaniosis, but they are apparently not very effective in dogs. Goodwin and Rollo (1955) reviewed the chemotherapy of leishmaniosis briefly.
Control: Prevention of leishmanial infections depends on breaking the life cycle by elimination of sandflies. This can be done by residual spraying of houses, barns and outside resting places with DDT or other chlorinated hydrocarbon insecticides (Hertig, 1949; Corradetti, 1954; Deane, 1958). In addition, insect repellents such as dimethylphthalate can be rubbed on the skin, houses can be screened with very fine mesh wire, and decaying vegetation and other breeding places can be cleaned up. In regions where kala-azar is a zoonosis, treatment of infected dogs and destruction of strays will eliminate the reservoir of infection for man.