The Blood Flagellates 577 



Symptoms and pathology. Kala-azar is a chronic or sub-acute disease 

 characterized by enlargement of the liver and spleen and by an irregular 

 fever, anemia, and leucopenia. Mortality is high in untreated cases. The 

 disease is more severe in epidemic outbreaks than in intervening periods, 

 and effects on a population may be aggravated by famine and by other 

 diseases. The incubation period varies from about 10 days to two or three 

 months as a rule (10), although incubation periods in U. S. troops during 

 AVorld War II ranged from three weeks to 19 months (42). 



A common early symptom is a high fever preceded by rigors. The fever 

 may become continuous or may be intermittent and irregular. Early en- 

 largement of the liver and spleen is typical, and the swelling usually 

 increases during the course of the disease. After emaciation becomes 

 marked in children, splenomegaly often produces a swollen protruding 

 abdomen. Grayish discoloration of the skin, especially over the forehead 

 and temples and sometimes around the mouth, is characteristic of chronic 

 cases. Eventually, a low fever becomes more or less continuous and ex- 

 tensive loss of weight occurs. 



The spleen, liver, and bone marrow are affected in practically all cases. 

 The extent to which other organs are involved is determined by length 

 and severity of the infection. Normal splenic tissues may be partly re- 

 placed by macrophages, and fibrous tissue of the reticulum may increase. 

 Effects on the liver are similar. Kiipffer's cells, which increase in number, 

 are often loaded with leishmanial forms, and there may be an increase 

 in fibrous tissue with marked cirrhosis in chronic cases. In the bone 

 marrow, as much as three-fourths of the normal tissue may be replaced 

 by packed macrophages, so that the production of blood cells is greatly 

 reduced. Consequently, some degree of anemia is to be expected, although 

 the red cell count seldom falls below 2,500,000. In addition, there is fre- 

 quently a leucopenia with a count well below 4,000, and a granulopenia 

 also has been noted. In the intestinal mucosa, multiplication of macro- 

 phages sometimes distends the villi. 



Multiplication of macrophages in the lymph glands, kidneys, testes, 

 lungs, heart, and adrenals is usually not extensive; accordingly, the para- 

 sites are to be expected primarily in isolated phagocytes. However, adreno- 

 cortical hypofimction, presumably a result of tissue destruction, has been 

 observed and may be correlated with skin pigmentation and low blood 

 pressure (15). 



Skin nodules, similar to non-ulcerating lesions of oriental sore, some- 

 times appear in treated patients about two years or so after clinical re- 

 covery (1, 9). The nodules, usually small, appear most commonly on the 

 face and neck. Beneath the thin epithelium there is an oedematous 

 dermis showing atrophy of connective tissue. Surrounding this area there 

 is a zone of fibroblasts and multiplying macrophages, the latter often 

 containing parasites. Such lesions may form a lasting reservoir of infec- 



