TY - JOUR
T1 - Efficacy and safety of single-dose liposomal amphotericin B for visceral leishmaniasis in a rural public hospital in Bangladesh
T2 - A feasibility study
AU - Mondal, Dinesh
AU - Alvar, Jorge
AU - Hasnain, Md Golam
AU - Hossain, Md Shakhawat
AU - Ghosh, Debashis
AU - Huda, M. Mamun
AU - Nabi, Shah Golam
AU - Sundar, Shyam
AU - Matlashewski, Greg
AU - Arana, Byron
N1 - Funding Information:
We are thankful to the Neglected Tropical Diseases–World Health Organization and the Agencia Española de Cooperación Internacional for the financial support for this study. icddr,b acknowledges with gratitude the commitment of these donors to its research efforts. We greatly appreciate the kind support of the Disease Control Unit, Directorate General of Health Services, and the Government of Bangladesh for conducting this study in the Muktagacha subdistrict hospital. We are grateful to the management, doctors, and nurses of the Muktagacha subdistrict hospital for diagnosis and treatment of study patients. We also express our high gratitude to the study participants. We thank Varalakshmi Elango who trained the study and hospital staff in GCP and was the external international monitor of the study.
PY - 2014/1
Y1 - 2014/1
N2 - Background: To rapidly reduce the burden of visceral leishmaniasis for national elimination programmes, an acceptable, safe, and effective treatment is needed that can be delivered at primary health-care centres. We aimed to assess the tolerability, safety, and cure rate of single-dose liposomal amphotericin B (AmBisome, Gilead, USA) for visceral leishmaniasis treatment in such a setting in Bangladesh. Methods: We enrolled patients who had been diagnosed with visceral leishmaniasis at Muktagacha upazila (subdistrict) hospital, Bangladesh. Eligible participants were at least 5 years old and had a history of fever for more than 2 weeks, splenomegaly, rK39 rapid test positivity, and haemoglobin concentrations of at least 50 g/L. Participants were provided a one-off intravenous infusion of liposomal amphotericin B (10 mg/kg bodyweight). Clinical assessments were done during treatment, before hospital discharge, and on days 30 and 180 after treatment. Cure was defined as resolution of fever, decrease in spleen size, and an increase in haemoglobin by 10% compared with baseline or to at least 100 g/L. We estimated efficacy in terms of initial cure (at day 30) and final cure (at 6 months), and safety in all patients who were enrolled (intention-to-treat analysis). We also assessed efficacy in all patients who completed treatment and 6 month follow-up after treatment with or without visceral leishmaniasis relapse (per protocol analysis). We assessed acceptability in terms of proportion of patients who consented to treatment. This study was registered with the Australian New Zealand Clinical Trial Registry, number CTRN12612000367842. Findings: Between March 5, and Aug 14, 2012, 329 (55%) of 594 cases of suspected visceral leishmaniasis were confirmed. Of these cases, five patients did not consent to treatment and 24 were ineligible for treatment. In the intention-to-treat analysis, 261 (87%) of 300 patients achieved initial cure and 290 (97%) achieved final cure. In the per-protocol analysis, 260 (88%) of 296 patients achieved initial cure and 289 (98%) achieved final cure. One patient did not start treatment owing to an allergic reaction to liposomal amphotericin B. During treatment or within 2 h afterwards, 79 (26%) patients developed fever, 109 (36%) had fever with rigor, and 56 (19%) had hypotension. No patients needed referral to a tertiary hospital for management of adverse events. Interpretation: Treatment of visceral leishmaniasis in a primary health-care facility with single-dose liposomal amphotericin B could safely and effectively be adopted by the national visceral leishmaniasis elimination programme in Bangladesh. Funding: Neglected Tropical Diseases (WHO), Agencia Española de Cooperación Internacional.
AB - Background: To rapidly reduce the burden of visceral leishmaniasis for national elimination programmes, an acceptable, safe, and effective treatment is needed that can be delivered at primary health-care centres. We aimed to assess the tolerability, safety, and cure rate of single-dose liposomal amphotericin B (AmBisome, Gilead, USA) for visceral leishmaniasis treatment in such a setting in Bangladesh. Methods: We enrolled patients who had been diagnosed with visceral leishmaniasis at Muktagacha upazila (subdistrict) hospital, Bangladesh. Eligible participants were at least 5 years old and had a history of fever for more than 2 weeks, splenomegaly, rK39 rapid test positivity, and haemoglobin concentrations of at least 50 g/L. Participants were provided a one-off intravenous infusion of liposomal amphotericin B (10 mg/kg bodyweight). Clinical assessments were done during treatment, before hospital discharge, and on days 30 and 180 after treatment. Cure was defined as resolution of fever, decrease in spleen size, and an increase in haemoglobin by 10% compared with baseline or to at least 100 g/L. We estimated efficacy in terms of initial cure (at day 30) and final cure (at 6 months), and safety in all patients who were enrolled (intention-to-treat analysis). We also assessed efficacy in all patients who completed treatment and 6 month follow-up after treatment with or without visceral leishmaniasis relapse (per protocol analysis). We assessed acceptability in terms of proportion of patients who consented to treatment. This study was registered with the Australian New Zealand Clinical Trial Registry, number CTRN12612000367842. Findings: Between March 5, and Aug 14, 2012, 329 (55%) of 594 cases of suspected visceral leishmaniasis were confirmed. Of these cases, five patients did not consent to treatment and 24 were ineligible for treatment. In the intention-to-treat analysis, 261 (87%) of 300 patients achieved initial cure and 290 (97%) achieved final cure. In the per-protocol analysis, 260 (88%) of 296 patients achieved initial cure and 289 (98%) achieved final cure. One patient did not start treatment owing to an allergic reaction to liposomal amphotericin B. During treatment or within 2 h afterwards, 79 (26%) patients developed fever, 109 (36%) had fever with rigor, and 56 (19%) had hypotension. No patients needed referral to a tertiary hospital for management of adverse events. Interpretation: Treatment of visceral leishmaniasis in a primary health-care facility with single-dose liposomal amphotericin B could safely and effectively be adopted by the national visceral leishmaniasis elimination programme in Bangladesh. Funding: Neglected Tropical Diseases (WHO), Agencia Española de Cooperación Internacional.
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U2 - 10.1016/S2214-109X(13)70118-9
DO - 10.1016/S2214-109X(13)70118-9
M3 - Article
C2 - 25104636
AN - SCOPUS:84890857397
SN - 2214-109X
VL - 2
SP - e51-e57
JO - The Lancet Global Health
JF - The Lancet Global Health
IS - 1
ER -
