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Amphotéricine B/usage thérapeutique , Collecte de données/méthodes , Humains , Inde/épidémiologie , Diffusion de l'information , Leishmaniose viscérale/traitement médicamenteux , Leishmaniose viscérale/épidémiologie , Leishmaniose viscérale/prévention et contrôle , Phosphoryl-choline/analogues et dérivés , Phosphoryl-choline/usage thérapeutique , Prévention primaire/méthodesRésumé
The communication presents clinical response of cases of visceral leishmaniasis to treatment by two different brands of Amphotericin B. FungizoneTM was found to be slightly better than Amphotericin BTM, however, the difference is not statistically significant.
Résumé
BACKGROUND & OBJECTIVE: Of the two reservoirs of infection of kala-azar i.e., patients of kala-azar and post kala-azar dermal leishmaniasis (PKDL), PKDL provides easy access for the sandfly to pick up the parasites. In the last epidemic of 1977 in India, the importance of PKDL as a potential cause of increase in number of kala-azar cases was ignored. During recent years, we found an increase in the cases of kalaazar whereas cases of PKDL were decreasing in Bihar. We undertook this study to find out reasons for this phenomenon. METHODS: These three different settings were selected to study the trends of the disease. (i) Cases of PKDL registered in the Dermatology Department of Patna Medical College Hospital (PMCH), one of the largest and oldest teaching hospital in Bihar, between 1970 and 2005; (ii) Rajendra Memorial Research Institute of Medical Sciences, Patna (RMRIMS), a research institute exclusively devoted to kala-azar (2000 and 2005); and (iii) interviews with two leading dermatologists of Patna selected by lottery on the incidence of PKDL and possible causes of its decrease, if any. The number of cases of kala-azar (visceral leishmaniasis, VL) from Bihar was studied from Malaria Departments of the Government of Bihar and Government of India, the two nodal departments dealing with the kala-azar. RESULTS: Analysis of data from Dermatology Department of PMCH showed increase in number of cases of PKDL from two in 1970 to 12 in 1976, a year before the first epidemic of kala-azar in 1977 with 100,000 cases. Kala-azar cases decreased to 11,120 in 1982 due to control measures taken between 1977- 1979 but cases of PKDL reached 28 and kept on increasing. During 1950 to 1977, low dose and short duration regimen of sodium antimony gluconate (SAG) was mainly used in the treatment of kala-azar. Between 1977-1991 increasing incidence of unresponsiveness to SAG, led to the usage of longer duration and higher dose regimen of SAG, more use of amphotericin B (AMB) for SAG resistant cases and also as a first line drug for kala-azar and PKDL. The number of kala-azar cases started decreasing after control measures taken during 1992-1994 but cases of PKDL continued decreasing. The effect of control measures on the incidence of kala-azar was visible upto 2002, but decrease in number of PKDL cases continued. In 2005 the number of PKDL cases was 14 but number of kala-azar cases reached 21,177 in Bihar. In the interview, the two dermatologists also opined that PKDL was decreasing due to increased use of amphotericin B in the treatment of kala-azar. Trend analysis done on the data of PMCH and RMRIMS showed that PKDL will decrease in coming years and kala-azar will increase. INTERPRETATION & CONCLUSION: Incidence of PKDL decreased in PMCH and RMRIMS and also suggested by two dermatologists that extensive use of amphotericin B in the treatment of kala-azar might be responsible for decrease in number of cases of PKDL.
Sujets)
Amphotéricine B/usage thérapeutique , Antiprotozoaires/usage thérapeutique , Épidémies de maladies/statistiques et données numériques , Humains , Incidence , Inde/épidémiologie , Leishmaniose viscérale/traitement médicamenteuxRésumé
BACKGROUND & OBJECTIVE: Present treatment strategies for kala-azar (visceral leishmaniasis, VL) include use of first line drug sodium antimony gluconate (SAG) to all patients but a large number of patients do not get relief with this drug. If a patient does not respond to a full course of SAG, a second or third line drug is given. We undertook this study to test whether an improved outcome can be achieved by employing a strategy of treatment based on culture and sensitivity of amastigotes to SAG compared with conventional empirical treatment. METHODS: In a double-blind, randomized, controlled trial done in Balaji Utthan Sansthan, Patna, of the 181 patients screened,140 were finally randomly allocated to two groups A and B; group A patients were treated with SAG if their amastigotes were sensitive to SAG, and all patients in group B were treated with SAG to start with. Primary outcome measured was as no relapse within 6 months of follow up after cure and other outcomes measured were period of stay of patients in hospital, expenditure involved in the treatment, and infectivity periods of two groups, two-third of treatment period and whole of untreated period were taken as infectivity period. SAG was used at a dosage of 20 mg/kg given deep intramuscular injections in buttock for 28 days, amphotericin B (AMB) given at a dose of 1 mg/kg body wt daily for 20 days as a slow intravenous infusion in 5 per cent dextrose. RESULTS: Of the 70 patients in group A, 29 patients whose amastigotes were sensitive to SAG were treated with SAG, 2 patients were withdrawn due to drug toxicity; and 2 relapsed within 6 months of follow up and ultimate cure occurred in 25 (86.2%) patients only. Of the 70 patients in group B treated with SAG, 5 (7.1%) patients withdrew due to drug toxicity, 35 patients (50%) did not respond to treatment, 5 (7.1%) relapsed during 6 months of follow up and thus only 25 patients (35.7%) were ultimately cured. The difference between the two groups was significant (P<0.001). No patient died during treatment due to any toxicity because of early withdrawal of patients from treatment apprehending toxicity. Patients whose amastigotes were resistant to SAG, withdrawn from the study due to SAG toxicity, relapsed after cure with SAG, and who did not respond to SAG in both the groups were treated with AMB and all were cured. Groups B and A patients spent 3065 and 2340 days respectively in hospital, group B 1.3 times more than group A. The likely period of spread of parasites in society was 1965 days in group B and 1644 days in group A, group B 1.4 times more than group A. The total expenditure on treatment in groups B and A was dollars 65,575 and dollars 50,590 respectively; group B patient had to spend 1.3 times more than group A. INTERPRETATION & CONCLUSION: A new strategy for treatment of kala-azar based on culture and sensitivity of amastigotes improved the cure rate, saved expenditure on the patient's treatment, patients had to stay for shorter periods in hospital and reduced the chance of spread of SAG resistant disease in society. Till the government opts for better drugs, the treatment based on culture and sensitivity of the parasites to SAG may be a better method.
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Adolescent , Adulte , Sujet âgé , Amphotéricine B/usage thérapeutique , Animaux , Gluconate d'antimoine et de sodium/usage thérapeutique , Antiprotozoaires/usage thérapeutique , Enfant , Enfant d'âge préscolaire , Méthode en double aveugle , Résistance aux substances , Femelle , Humains , Inde , Leishmania donovani/effets des médicaments et des substances chimiques , Leishmaniose viscérale/traitement médicamenteux , Macrophages/parasitologie , Mâle , Adulte d'âge moyenRésumé
Paromomycin, an aminoglycoside, is known to cause several side effects like nephrotoxicity and ototoxicity like other aminoglycosides but tetany has not been reported. Three cases of tetany were detected in the patients of kala-azar treated with paromomycin. They were promptly treated with intravenous 10 per cent calcium gluconate and tetany was relieved immediately and treatment with paromomycin continued with oral calcium supplement. After completion of 21 days treatment with paromomycin patients' splenic aspirates were free of parasites. Paromomycin may cause temporary tubular damage leading to calcium wasting in urine and hypocalcaemia resulting in tetany. Prompt detection of symptoms and intravenous calcium gluconate treatment promptly reverse the situation.
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Adolescent , Antibactériens/effets indésirables , Calcium/métabolisme , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Leishmaniose viscérale/traitement médicamenteux , Mâle , Paromomycine/effets indésirables , Essais contrôlés randomisés comme sujet , Tétanie/induit chimiquementRésumé
BACKGROUND & OBJECTIVE: Bihar State of India has been an endemic State for kala-azar. There has been many phases of DDT sprays for vector control. An outbreak of kala-azar occurred in Goanpura, 6 km from Patna, Bihar, in 2003. We undertook this study with a new approach of kala-azar elimination in this village with priority to treatment of cases followed by supplementation with supervised DDT spray for vector control. METHODS: This study included a camp approach to collect patients at in the camp, screening of patients with rK-39, transporting the patients to the hospital of Balaji Utthan Sansthan, Patna, Bihar, confirming the diagnosis by demonstration of Leishman-Donovan (LD) bodies in splenic aspirates after proper clinical and pathological investigations, and treatment with amphotericin B (Fungizone) at a dose of 1mg/kg body wt for 20 days. If parasites persisted after 20 days, five more infusions were given. The State Government was persuaded to do supervised DDT spray as per the guidelines. All patients were followed up for 6 months for any relapse, and the village of Goanpura for 3 years for occurrence of any new case. RESULTS: A camp was held in that village on September 11, 2003 after due publicity. A total of 368 patients having different ailments, attended the camp; 25 patients were screened with rk-39 for kala-azar and 21 patients gave positive results. All 21 patients were shifted to Balaji Utthan Sansthan for treatment. After thorough clinical examination and pathological tests splenic aspiration was done. All 21 patients were positive for LD bodies. One patient died and the remaining 20 completed full course of treatment and were cured. No patients relapsed within six months of follow up. Two rounds of supervised DDT spray were done. No new case occurred in the village during three years of follow up. No sandfly was detected in the village during the years of follow up. INTERPRETATION & CONCLUSION: Camp strategy to collect patients at one place, screening of patients with rk-39, transporting rk-39 positive patients to the hospital, treatment with an effective drug amphotericin B with no incidence of unresponsiveness and relapsed minimized transmission of the disease; only two rounds of supervised intensive spray of DDT eliminated sandflies from the village. This new cost effective approach in which treatment of patients was done with an effective drug followed by supervised DDT spray may be adopted for elimination of kala-azar from Bihar.
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Amphotéricine B/usage thérapeutique , Animaux , Antiprotozoaires/usage thérapeutique , DDT , Humains , Inde/épidémiologie , Vecteurs insectes , Leishmania donovani , Leishmaniose viscérale/traitement médicamenteux , Psychodidae/parasitologie , Rate/parasitologieRésumé
Sodium antimony gluconate (SAG) and miltefosine used in the treatment of kala-azar are known to cause several side effects but severe thrombocytopenia has not been reported. Four cases of severe thrombocytopenia, two caused by SAG and two by miltefosine were promptly detected and treated by immediate withdrawal of the offending drugs, platelet and blood transfusions and dexamethasone. After improvement Leishman-Donovan (LD) bodies were demonstrated in splenic aspirates of both patients of SAG group and one of miltefosine and they were treated with 1 mg/kg body wt of amphotericin B for 20 days and cured. One patient of miltefosine group treated outside only on the basis of rK-39 positivity did not show LD bodies in splenic aspirates and improved without any antikala- azar drug. None of the patients relapsed within 6 months of follow up. Prompt detection of side effects under the concept of pharmacovigilance can save life of such patients.
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Adolescent , Adulte , Gluconate d'antimoine et de sodium/effets indésirables , Antiprotozoaires/effets indésirables , Femelle , Humains , Leishmaniose viscérale/traitement médicamenteux , Mâle , Phosphoryl-choline/effets indésirables , Thrombopénie/induit chimiquementRésumé
BACKGROUND & OBJECTIVES: Sodium antimony gluconate (SAG) is reported to be losing its efficacy in Bihar as a first line drug for treatment of visceral leishmaniasis (VL). Concerned with the increasing incidence of antimony-resistant VL patients in Bihar, we undertook an epidemiological, clinical and pharmacological study to formulate a scientific basis for choosing a suitable first line drug for VL. METHODS: Consecutive, fresh and parasitologically confirmed patients of VL from different geographical areas of Bihar were considered for inclusion in the study. Parasites isolated from patients were tested in vitro to assess their response to sodium antimony gluconate (SAG) to 20 microg/ml, response to 20 mg/kg of SAG for 5 days in experimentally induced VL in BALB/c mice from those isolates, and response to SAG in patients treated with SAG for 28 days. Similarly response in culture (1 microg/ml) to amphotericin B (AMB) of all 282 isolates, (1 mg/kg body wt for 20 days) in patients and infected BALB/c mice (1 mg/kg body wt for 5 days) was determined. Antimony levels of plasma were determined at 2, 8 and 24 h after intramuscular injection of SAG. Patients unwilling for SAG treatment or relapsed after SAG treatment and withdrawn from SAG group because of toxicity were treated with AMB. Plasma antimony levels were estimated by atomic absorption spectrometer. RESULTS: Though antimony sensitive and resistant patient were distributed in all 14 districts of Bihar studied, there was a significant variation from district to district. Of the 123 patients included in the SAG treatment group, 19 were withdrawn due to development of toxicity and 2 died; 178 patients were treated with AMB. No patient in AMB group developed any toxicity or died. Only 47 (46%) of 102 patients, 106 (37.6%) of 282 infected macrophages, 90 (52.9%) of 170 experimental infections were cured with SAG. Mc Nemar's test on paired comparisons showed statistical significance difference (P<0.01) between infected macrophage and experimental infection. AMB cured all patients, infected mice and cleared parasites from all isolates. INTERPRETATION & CONCLUSION: Antimony resistant strains of L. donovani were wide spread over different geographical areas in Bihar. SAG cured lesser percentage of VL cases clinically compared to AMB and should be replaced by AMB as a first line drug.
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Adulte , Amphotéricine B/usage thérapeutique , Analyse de variance , Animaux , Antimoine/sang , Gluconate d'antimoine et de sodium/usage thérapeutique , Antiprotozoaires/usage thérapeutique , Enfant , Résistance aux substances/physiologie , Humains , Inde/épidémiologie , Leishmaniose viscérale/traitement médicamenteux , Mâle , Souris , Souris de lignée BALB C , Spectrophotométrie atomiqueRésumé
BACKGROUND & OBJECTIVES: In a kala-azar endemic area in rural Bihar with a large number of patients unresponsive to sodium antimony gluconate and pentamidine, treatment with amphotericin B was tried in a rural set-up with the objective to cure these patients, and to assess whether such a centre could be run successfully in a rural set-up. METHODS: After thorough clinical examination and biochemical investigations, parasitologically confirmed patients who had haemoglobin above 5 g/dl, electrolyte imbalance if any, corrected, and ECG changes suggestive of myocardial damage stabilised after 10 days of bed rest were treated. Amphotericin B deoxycholate was infused at a dose of 1 mg/kg body weight, daily for 20 days. The adverse events were closely monitored. RESULTS: All 7 (100%) untreated patients of kala-azar, 258 (97%) of the 266 antimony and pentamidine resistant patients, and 31 (86%) of the 36 patients who had relapsed after a low dose regimen of amphotericin B, were cured with 20 infusions of amphotericin B. Eight (3%) patients of the antimony and pentamidine resistant group and 5 (14%) patients who had relapsed after low dose amphotericin B regimen required 25 infusions of amphotericin B to achieve parasitological cure. INTERPRETATION & CONCLUSIONS: With some precautions and proper management, all patients of kala-azar could be cured with amphotericin B in a rural set-up. A significant (P < 0.05) percentage of patients of group C relapsing after a low dose amphotericin B regime requiring 25 infusions for cure suggests that an adequate dose regime of amphotericin B should be given during the first course of treatment to prevent emergence of drug resistance.
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Adolescent , Adulte , Amphotéricine B/usage thérapeutique , Antiprotozoaires/usage thérapeutique , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Inde , Nourrisson , Nouveau-né , Leishmaniose viscérale/traitement médicamenteux , Mâle , Adulte d'âge moyen , Services de santé rurauxRésumé
One hundred thirty parasitologically confirmed cases of kala-azar were randomly divided in two equal treatment groups. Patients in group A were treated by infusion with amphotericin B deoxycholate (ABD), 1 mg/kg day on days 1-20 and the infusion was given in two hours. Patients in group B were treated by an escalating dose of ABD 0.05 mg/kg, 0.1 mg/kg, 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg on days 1-5, respectively and then in the same dosage on alternate days. The infusion was completed in 6 hours. Total dose of 20 mg/kg remaining the same in both the groups, the treatment was completed in 20 days in group A and 43 days in group B. Clinical cure (subsidence of fever, improvement in general well being and regression in the size of the spleen) and parasitological cure (absence of parasites in splenic aspirates at the end of treatment) occurred in all patients in both the groups. Sixty four (99%) patients in each group had not relapsed clinically and parasitologically within 6 months of follow up and were ultimately cured. The two relapsed patients, one in each group were treated with a 20-day course of ABD and were cured. Leukocyte count, haemoglobin, serum albumin increased (P < 0.05) and ESR, spleen and liver size decreased (P < 0.05) at the end of treatment and follow up. Adverse events were similar in both the groups. The minimum cost of treatment estimated was Rs. 14,500 in group B and Rs. 10,000 in Group A. Thus the newer mode of administration was more cost effective. CONCLUSION: It was concluded that newer mode of administration of amphotericin B was as effective and tolerable as the classical mode of administration and was no more toxic. The newer mode of administration of amphotericin B is more cost effective and puts lesser burden on hospital staff and is recommended for use in kala-azar.
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Adolescent , Adulte , Amphotéricine B/administration et posologie , Antiprotozoaires/usage thérapeutique , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Nourrisson , Leishmaniose viscérale/traitement médicamenteux , Mâle , Adulte d'âge moyen , Études prospectivesRésumé
In a prospective study, 80 cases of fever with hepatosplenomegaly, anemia and leucopaenia coming from the hyperendemic zones for visceral leishmaniasis of North-Bihar, India were screened and subjected to bone marrow or splenic puncture for demonstration of Leishman-donovan bodies (LDB) and DIRECT AGGLUTINATION TEST (DAT) with antigen prepared by Harith et al. 59 cases were confirmed for Visceral Leishmaniasis (VL) by demonstration of LDB in which DAT was also positive in different titres ranging from 1:1600 onwards. Out of 21 cases in which the bone marrow was negative for parasite, DAT was positive in 10 cases. 8 Out of 10 cases responded to WHO regimen of treatment with sodium stibogluconate (SSG). Remaining two cases who did not respond to this therapy became positive for parasites on subsequent splenic aspirate. They were treated with pentamidine isethionate and were cured. 11 out of 80 cases showing a titre of 1:400 or lower in DAT, 6 proved to be cases of enteric fever and 5 of malaria. Thus DAT using Harith's antigen was found to be 100% sensitive and specific in detection of early cases of Indian VL.
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Adulte , Tests d'agglutination/méthodes , Femelle , Humains , Inde/épidémiologie , Leishmaniose viscérale/diagnostic , Mâle , Études prospectives , Sensibilité et spécificitéRésumé
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.
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Adolescent , Adulte , Amphotéricine B/administration et posologie , Antibactériens/administration et posologie , Enfant , Enfant d'âge préscolaire , Acide désoxycholique/administration et posologie , Relation dose-effet des médicaments , Calendrier d'administration des médicaments , Association médicamenteuse , Femelle , Humains , Leishmaniose viscérale/traitement médicamenteux , Mâle , Adulte d'âge moyen , Résultat thérapeutiqueRésumé
Arrhythmias and cardiac arrest have been reported during amphotericin B administration but no effective technique has been described to prevent them. I saw two patients with kala-azar resistant to sodium stibogluconate who developed cardiac arrest after amphotericin infusion (in spite of tolerating a test dose). Both had low levels of serum sodium, potassium and calcium. After these were corrected the amphotericin B was restarted and the course of treatment completed successfully. I suggest that prior to giving amphotericin B to patients with resistant kala-azar their electrolyte imbalance should be corrected.
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Adulte , Amphotéricine B/effets indésirables , Troubles du rythme cardiaque/étiologie , Calcium/sang , Enfant , Femelle , Arrêt cardiaque/étiologie , Humains , Leishmaniose viscérale/traitement médicamenteux , Mâle , Potassium/sang , Sodium/sang , Troubles de l'équilibre hydroélectrolytique/sangRésumé
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.
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Adulte , Amphotéricine B/usage thérapeutique , Femelle , Humains , Leishmaniose viscérale/traitement médicamenteux , Grossesse , Complications parasitaires de la grossesse/traitement médicamenteuxRésumé
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)
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Adolescent , Adulte , Amphotéricine B/administration et posologie , Gluconate d'antimoine et de sodium/administration et posologie , Femelle , Humains , Inde , Leishmaniose viscérale/traitement médicamenteux , MâleRésumé
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.