One-year follow-up of immunocompetent male patients treated with miltefosine for primary visceral leishmaniasis in Bihar, India.

TO THE EDITOR—We read with interest the 2 recent publications [1, 2] investigating the current efficacy of miltefosine in the treatment of visceral leishmaniasis (VL) in the Indian subcontinent. Since 2007, Médecins Sans Frontières (MSF) has been working in Bihar, India, and has treated >9000 patients with VL using liposomal amphotericin B (Ambisome, Gilead Pharmaceuticals). However, in November 2011 MSF experienced a critical shortage of Ambisome lasting 12 weeks. An operational strategy to reserve Ambisome for patients with the most clinically severe disease and women of childbearing age was implemented during this period, which took into account the recommendation of 5 months of compulsory contraceptive coverage for women of reproductive age taking 28 days of oral miltefosine [3], which MSF could not guarantee. During this shortage, all male patients aged >5 years with a clinical history of primary VL (fever ≥2 weeks with clinical splenomegaly), positive rK39 assay, and negative human immunodeficiency virus (HIV) test who were clinically stable (hemoglobin level >5 g/dL, no obvious coinfections, and able to receive ambulatory treatment) were treated with 28 days of oral miltefosine as per current Indian government guidelines (100 mg daily for >25 kg, 50 mg for ≤25 kg, and 2.5 mg/kg daily for patients <12 years). Treatment was ambulatory with weekly visits for review and drug blister distribution/collection maintained throughout treatment to ensure compliance. One hundred twenty-four patients were initiated on treatment, of whom 1 (0.8%) died and 4 (3.2%) defaulted during the 28-day treatment regimen. Initial cure was defined as improvement of symptoms, cessation of fever, and >50% reduction in spleen size by the end of treatment. Test of cure was reserved for suspected treatment failures. Initial cure was achieved in all remaining patients (119 [96%]), although 7 patients displayed complete resolution of symptoms by end of treatment without achieving >50% reduction in spleen size. Final cure was defined as absence of signs and symptoms of VL by 6 and/or 12 months following treatment completion. All patients with suspected relapse had splenic or bone marrow aspirate confirmation of presence of parasites. The final cure results are presented in Table 1. The mean time to relapse was 114 days (SD, 75 days; range, 65–317 days). Of note, 7 of 119 (5.9%) patients relapsed within 6 months of completing treatment, with 2 (1.7%) more relapsing between 6 and 12 months following completion of treatment. Therefore, the total relapse rate at 12 months was 7.6%. None of the patients who failed to achieve >50% reduction of spleen size by end of treatment relapsed. The proportion of patients who had relapsed at 6 months was similar to the 6.8% reported by Sundar et al in Bihar [1], but less than the 10.8% reported by Rijal et al in Nepal [2]. However, in our cohort, the proportion who relapsed between 6 and 12 months following treatment (1.7% [2 of 119]) was higher than that reported by Sundar Table 1. Sixand 12-Month Outcomes