Randomised controlled trial of aminosidine (paromomycin) v sodium stibogluconate for treating visceral leishmaniasis in North Bihar, India

Kala-Azar Research Centre Muzaffarpur, Brahmpura, Muzaffarpur, Bihar, India.
BMJ Clinical Research (Impact Factor: 14.09). 05/1998; 316(7139):1200-5.
Source: PubMed

ABSTRACT To assess the efficacy and tolerability of aminosidine compared with sodium stibogluconate for treating visceral leishmaniasis.
Randomised, unblinded, controlled trial with 180 day follow up.
Kala-Azar Research Centre, Brahmpura, Muzaffarpur, Bihar, India.
People of either sex aged 6-50 years with symptoms and signs suggestive of visceral leishmaniasis (fever, loss of appetite, enlarged spleen) with leishmania amastigotes detected in Giemsa stained aspirates of spleen or bone marrow.
Aminosidine at three daily doses (12, 16, and 20 mg/kg) for 21 days and sodium stibogluconate 20 mg/kg/day for 30 days.
Laboratory measures of efficacy: parasite count, haemoglobin concentration, white cell count, platelet count, serum albumin concentration. Clinical measures of efficacy: spleen size, fever, body weight, and liver size. Measures of safety: liver and renal function tests, reports of adverse events.
Of the 120 patients enrolled (30 per treatment arm), 119 completed treatment and follow up. Cure at end of follow up was achieved in 23 (77%), 28 (93%), and 29 (97%) patients treated with 12, 16, and 20 mg aminosidine/kg/day respectively, and in 19 (63%) patients given sodium stibogluconate. At 16 and 20 mg/kg/day, aminosidine was significantly more active than sodium stibogluconate in both clinical and laboratory measures of efficacy. No significant clinical or laboratory toxicity occurred in any treatment group.
A 21 day course of aminosidine 16 or 20 mg/kg/day should be considered as first line treatment for visceral leishmaniasis in Bihar.

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    • "In 2002, it was first introduced as anti-leishmanial drug in the form of PM sulphate.[22] Low cost, fewer side-effects, better efficacy and shorter duration of administration make this drug popular and thought to be a candidate for the first line therapy for VL patients.[23242526] It belongs to the aminoglycoside group of antibiotic; hence, the mechanism of action is by inhibition of protein synthesis. "
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    03/2014; 4(1):4-9. DOI:10.4103/2229-5070.129142
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    • "In addition to this, paromomycin showed a lower incidence of side effects, which included ototoxicity and renal toxicity. For this reason, it was concluded from this study that paromomycin was an adequate second-line treatment in cases resistant to antimonials [88]. These results led to the development of a phase III trial in Bihar from 2003 to 2004, where paromomycin was not inferior to amphotericin B deoxycholate, with final cure rates of 94.6 versus 98.8 %, respectively [89]. "
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    • "This alarming situation intensified research into the mechanisms by which Leishmania acquires resistance to drugs. Drug resistance in this organism (but also in Plasmodium and Entamoeba parasites as well as in neoplastic cells) is associated with a multidrug-resistant (MDR) phenotype characterized by the over-expression of a P-glycoprotein, Pgp 170 (130 to 200 kDa) [7], [8], [9]. It acts as a transmembrane efflux pump for a diverse group of lipophilic compounds, including many chemically diverse drugs and fluorescent dyes as well as calcium channel blockers [10], [11]. "
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