Comparison of regimens of amphotericin B deoxycholate in kala-azar.

A total of 288 parasitologically proved patients of kala-azar were randomly allocated to three treatment groups. Patients in groups A, B and C received amphotericin B (AMB) in a dose of 1 mg/kg body weight (bw)/day, 0.75 mg/kg bw/day and 0.5 mg/kg bw/day for 20 days respectively. Apparent cure (afebrile at the end of therapy) occurred in all patients and parasitological cure in 96 (100%), 92 (96%) and 84 (88%) patients respectively in groups A, B and C. Ultimate cure (no relapse in six months of follow up) occurred in 95 (99%), 87 (91%) and 79 (82%) patients in groups A, B and C respectively. The difference between the ultimate cure in the three groups was significant (P < 0.05). The incidence of adverse events (rise in serum creatinine and fall in serum potassium, loss of appetite and shivering, rigor and fever during infusion indicative of renal, GIT and infusion related toxicities respectively) was similar in the three groups. This study showed that amphotericin B should be given at a dosage of 1 mg/kg bw/day for 20 days for Indian kala-azar patients to minimise relapses and prevent development of drug unresponsiveness.

The treatment of kala-azar during pregnancy.

BACKGROUND. Kala-azar in pregnant women is difficult to treat because for them the two commonly used drugs, sodium stibogluconate and pentamidine, are not considered safe. We assessed the effect of amphotericin B on pregnancy, on the foetus and kala-azar. METHODS. Five pregnant women were administered amphotericin B at a dose of 1 mg/kg body weight daily starting with 0.5 mg/kg body weight till a total dose of 20 mg/kg body weight was given. The progress of pregnancy was monitored ultrasonographically and the mothers and children were followed for six months. RESULTS. All the 5 women were cured of the disease and there was no harmful effect on the children. CONCLUSION. Amphotericin B cures kala-azar during pregnancy with no harmful effects on the foetus.

Evaluation of amphotericin B as a first line drug in comparison to sodium stibogluconate in the treatment of fresh cases of kala-azar.

A total of 150 patients of kala-azar matched for age and sex and parasitologically proved were randomly allocated to two equal treatment groups. Patients in one group received amphotericin B(AMB) in a dose of 1 mg/kg body weight (BW) on alternate days starting with 0.05 mg/kg/bw on first day with daily increments, till a total dose of 20 mg/kg/bw was given; the patients in the second group received sodium stibogluconate (SAG) in the dose of 20 mg/kg/bw, im daily for 30 days. The efficacy, safety and cost-effectiveness of the two drugs were compared. Apparent cure (afebrile at the end of therapy) in 75 (100%) and 69 (92%) patients and ultimate cure (no relapse in six months of follow up) in 75 (100%) and 60 (80%) patients occurred in the AMB and SAG groups respectively. The difference between the ultimate cure in the two groups was significant (P < 0.001). Six (8%) and 9(12%) patients of SAG group showed primary (with no response to SAG during treatment) and secondary unresponsiveness (with no response to SAG after relapse) respectively and they were cured with amphotericin B.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphotericin B in resistant kala-azar in Bihar.

BACKGROUND. During the recent epidemic of kala-azar in Bihar, we identified a group of patients who were unresponsive to the two commonly used drugs--sodium stibogluconate and pentamidine. We evaluated the use of amphotericin B in these patients because it has been shown to be active in experimental animals against amastigotes and promastigotes, it has been found to be useful in South American patients and is now recommended by the World Health Organization as a second line drug. METHODS. We selected 300 patients who were unresponsive to sodium stibogluconate and pentamidine (out of 500 patients with kala-azar confirmed by demonstration of Leishmania donovani bodies in their splenic aspirates). Amphotericin B was given in a dose of 1 mg/kg body weight on alternate days starting with 0.05 mg/kg body weight with daily increments till a 1 mg dose was reached. A total dose of 20 mg/kg was given initially and repeated if the parasites persisted. The investigations done before and after treatment were splenic or bone marrow aspiration, measurement of the spleen and liver size, body weight, total and differential white cell counts, haemoglobin level, total serum protein, blood urea, serum creatinine, serum potassium, blood sugar, serum alanine and aspartate transaminase, electrocardiography and a chest X-ray. The efficacy of treatment was assessed at the end of treatment and after 6 months of follow up. RESULTS. After treatment with amphotericin B, 298 (99%) of the patients had been cured of their disease as evidenced by the disappearance of fever, reduction of hepatosplenomegaly, clearance of the parasites from the spleen and bone marrow and an absence of relapse on 6 months of follow up. Two hundred and sixty-eight (89%) patients required 1 g of the drug, 24 (8%) required 1.5 g and 6 (2%) required 2 g. All patients had shivering and fever during the infusion. Two had a cardiac arrest from which they could not be revived. Other complications included anorexia, stomatitis, jaundice, hypokalaemia and a rise in blood urea. However, these were only mild and improved after treatment was stopped. CONCLUSION. Amphotericin B is an effective drug for patients with kala-azar unresponsive to treatment with sodium stibogluconate and pentamidine, but it should be administered under close medical supervision.

Efficacy of amphotericin B in multi-drug resistant kala-azar in children in first decade of life.

Fifty children in the first decade of life, and suffering from multiple drug resistant kala-azar, confirmed by demonstration of amastigotes in aspirates of bone marrow or spleen were treated with amphotericin B in gradually increasing dosage to a total dose of 20 mg/kg. All patients had classical features of severe kala-azar, and had taken more than one course of antimony and pentamidine, and three patients had taken one additional course of ketoconazole besides many courses of antimony and pentamidine. The clinical response started just after first infusion in 8 patients, and the patients became afebrile. By 5th infusion, all looked better and 18 patients became afebrile. By 15th infusion all patients were afebrile and cheerful. Their spleens became smaller and body weights and total white cell counts increased. Forty eight patients had parasitological cure at the end of treatment, and only 2 patients required an additional 5 infusions for parasitological cure. All patients were ultimately cured. No one relapsed within six months of follow up. All patients had shivering, rigor and rise of temperature on the day of infusion, which could be minimized with prior administration of low dose of hydrocortisone, but could not be eliminated. Eighteen patients had loose motions during treatment, while 14 patients had decrease in appetite which improved quickly when the treatment was over. Fourteen patients had transient rise of blood urea, in six patients serum creatinine also increased and 16 patients had a minor fall in serum potassium.(ABSTRACT TRUNCATED AT 250 WORDS)