Liver morphology and function in visceral leishmaniasis (Kala-azar).

AIM: To study the morphology and function of the liver in visceral leishmaniasis (Kala-azar). METHODS: Percutaneous liver biopsy specimens from 18 patients with confirmed visceral leishmaniasis were examined under light and electron microscopy before and after treatment with pentovalent antimony. The tissue was also examined for hepatitis B surface and core antigens using immunoperoxidase staining. Liver function was investigated in nine patients before and after treatment. RESULTS: Specimens before treatment showed Kupffer cells and macrophages colonised by leishmania parasites in 40% of cases. A chronic mononuclear cell infiltrate had affected the portal tracts and lobules. Ballooning degeneration of the hepatocytes, fibrosis of the terminal hepatic venules, and pericellular fibrosis were common findings. The fibrosis was related to Ito cells transforming to fibroblast-like cells. None of the patients had hepatitis B infection. All patients had biochemical evidence of liver dysfunction before treatment. Liver function improved after treatment. CONCLUSION: Visceral leishmaniasis causes morphological and functional disturbance in the liver. Focal fibrosis rather than cirrhosis occurs. The exact aetiology of hepatic damage is unclear but may have an immunological basis.

The treatment of kala-azar in the Sudan with sodium stibogluconate: a randomized trial of three dosage regimens.

In a randomized study in the Sudan, 3 different regimens of sodium stibogluconate were compared in patients with parasitologically confirmed kala-azar (visceral leishmaniasis): 10 mg/kg for 30 d (38 patients), 20 mg/kg for 30 d (29 patients), and 20 mg/kg for 15 d (37 patients). Treatment failures were defined as death, partial response, relapse, or the development of post-kala-azar dermal leishmaniasis. The hazard ratio for failure of 20 mg/kg for 30 d vs. 10 mg/kg for 30 d 2.1 (95% confidence interval [CI] = 0.6, 7.6) and for 20 mg/kg for 15 d vs. 10 mg/kg for 30 d it was 1.7 (95% CI = 0.5, 6.1). No significant difference was detected between the 3 regimens in the rate of return to normal of haematological criteria, regression of spleen size, or weight gain. After 15 d treatment parasite clearance with 20 mg/kg for 30 d and 20 mg/kg for 15 d was more profound than with 10 mg/kg for 30 d (P < 0.05), but the difference was no longer present at the end of treatment. Further investigation of the effectiveness of short, intensive treatment regimens in the treatment of kala-azar is warranted.

Kala-azar: a comparative study of parasitological methods and the direct agglutination test in diagnosis.

In a comparative study 88 patients were diagnosed as suffering from kala-azar (visceral leishmaniasis) using 3 parasitological methods simultaneously. Splenomegaly was absent in 4 cases. In 84 patients with splenomegaly, splenic aspiration appeared to be the most sensitive method (96.4%), followed by bone marrow aspiration (70.2%) and lymph node aspiration (58.3%). There was no relation between titres in the direct agglutination test and parasite load as determined by the number of parasitological methods which were positive or parasite density in splenic aspirates. Splenic aspiration and bone marrow aspiration were compared as an assessment of cure in kala-azar. In 6 (13%) of 46 patients tested, parasites were found, all by splenic aspiration. Bone marrow showed parasites in one of these. The literature with regard to parasitological investigations before and after treatment is reviewed.

Oral leishmaniasis associated with kala-azar. A case report.

Mucosal leishmaniasis as an oral disease in the form of chronic periodontitis with involvement of the oral mucosa is described. Leishmania parasites were isolated from the oral lesions, lymph nodes, and bone marrow. The patient had a low-grade fever and hepatosplenomegaly that regressed along with the oral lesions after treatment with stibogluconate sodium.

Clinical aspects of kala-azar in children from the Sudan: a comparison with the disease in adults.

The clinical presentation of kala-azar in 43 children and 45 adults was compared. In both groups fever, left upper quadrant abdominal pain and swelling, and weight loss were equally the most common presenting symptoms. Lymphadenopathy was observed in 86 per cent of children and 76 per cent of adults. Splenomegaly was absent in 2 per cent of children and 7 per cent of adults. No significant difference was found in frequency distribution of symptoms and signs between children and adults. Haematological indices were compared in both children and adults with kala-azar and their control groups. In both children and adults with kala-azar, haemoglobin concentration, total white cell count, and platelet count were significantly lower before than after treatment. Only haemoglobin concentration was lower in children with kala-azar as compared with adults with the disease. Children in the control group had lower haemoglobin and higher total white cell count than adult controls. Response to therapy was evaluated in 693 patients. Two-hundred-and-fifty children and 373 adults were treated with sodium stibogluconate 10 mg/kg for 30 days; in both groups 12 per cent deaths and 4 per cent relapses occurred. Thirty children and 40 adults were treated with sodium stibogluconate 2 x 10 mg/kg for 15 days. In children, 3 per cent deaths and 7 per cent relapses were noted; in adults there were 8 per cent deaths and 5 per cent relapses. No significant difference in death rate or relapse rate was found between children and adults in both regimens. Both regimens performed equally well in children and adults with regard to death rate and relapse rate.

Direct agglutination test for diagnosis and sero-epidemiological survey of kala-azar in the Sudan.

132 patients with suspected kala-azar (visceral leishmaniasis) were included in a prospective study to compare the performance of the direct agglutination test (DAT) with smears of lymph node, bone marrow and splenic aspiration. A titre greater than 1:3200 was considered positive. 67 patients provided positive smears and 65 were smear-negative. Compared with the results obtained from smears, the sensitivity of the DAT was 94% and its specificity 72%. Of 18 patients who were negative by smears but positive by DAT, 3 were treated on strong clinical suspicion of kala-azar and responded well to therapy. One other patient had post-kala-azar dermal leishmaniasis. Of the remaining 14, 8 were tested with the leishmanin skin test; 6 gave a positive result, suggesting past or sub-clinical infection. In 4 smear-positive patients, the DAT was negative; in 2 of these, the test remained negative during 6 months' follow-up. In a sero-epidemiological survey in a camp for displaced people, 30 of 600 sampled individuals gave a positive DAT. Of these, 11 had been treated for kala-azar; 4 others were leishmanin positive. The DAT is a useful screening test (sensitivity 94%; predictive value of a negative test 92%), but it does not differentiate between past kala-azar, sub-clinical infection and active disease.

Kala-azar in displaced people from southern Sudan: epidemiological, clinical and therapeutic findings.

Six hundred and ninety-three patients with kala-azar were seen in Khartoum, Sudan, from January 1989 to February 1990. They were almost exclusively from the Nuer tribe, originating from the western Upper Nile province in southern Sudan, an area not known previously to be endemic for kala-azar. Because of the civil war in southern Sudan no treatment was available locally and massive migration to northern Sudan occurred; many died on the way. All age groups were affected; there was a slight male preponderance (56%). In the clinical presentation, marked generalized lymphadenopathy was prominent (84%). Splenomegaly was absent in 4% of cases. Patients usually showed anaemia, leucopenia and/or thrombocytopenia. 623 patients were treated with sodium stibogluconate, 10 mg/kg for 30 d; relapse occurred in 4% and death in 12%. Latterly, 70 patients were treated with sodium stibogluconate at 2 x 10 mg/kg for 15 d, with relapse in 6% and death in 6%. The difference between the 2 regimens in the number of relapses and deaths was not significant. The outbreak may have been caused by a combination of factors: the introduction of the parasite from an endemic area to a non-immune population, the presence of malnutrition caused by loss of cattle and unavailability of other food sources, and possibly an ecological change in favour of the sandfly vector.