Dinesh Mondal1, Jorge Alvar2, Md Golam Hasnain3, Md Shakhawat Hossain3, Debashis Ghosh3, M Mamun Huda3, Shah Golam Nabi4, Shyam Sundar5, Greg Matlashewski6, Byron Arana7. 1. International Centre For Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh. Electronic address: din63d@icddrb.org. 2. World Health Organization/Neglected Tropical Diseases, Geneva, Switzerland. 3. International Centre For Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh. 4. Directorate General of Health Services, Government of Bangladesh, Dhaka, Bangladesh. 5. Kala-azar Medical Research Centre, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. 6. Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada; UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland. 7. UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland.
Abstract
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.
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.
Authors: A C Vallur; A Hailu; D Mondal; C Reinhart; H Wondimu; Y Tutterrow; H W Ghalib; S G Reed; M S Duthie Journal: Eur J Clin Microbiol Infect Dis Date: 2014-11-19 Impact factor: 3.267