title: Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use.
abstract: BACKGROUND
  Miltefosine is the only oral drug available for treatment of Indian visceral leishmaniasis (VL), which was shown to have an efficacy of 94% in a phase III trial in the Indian subcontinent. Its unrestricted use has raised concern about its continued effectiveness. This study evaluates the efficacy and safety of miltefosine for the treatment of VL after a decade of use in India.
  
  
  METHODS
  An open-label, noncomparative study was performed in which 567 patients received oral miltefosine (50 mg for patients weighing <25 kg, 100 mg in divided doses for those weighing ≥25 kg, and 2.5 mg per kg for those aged <12 years, daily for 28 days) in a directly observed manner. Patients were followed up for 6 months to see the response to therapy.
  
  
  RESULTS
  At the end of treatment the initial cure rate was 97.5% (intention to treat), and 6 months after the end of treatment the final cure rate was 90.3%. The overall death rate was 0.9% (5 of 567), and 2 deaths were related to drug toxicity. Gastrointestinal intolerance was frequent (64.5%). The drug was interrupted in 9 patients (1.5%) because of drug-associated adverse events.
  
  
  CONCLUSIONS
  As compared to the phase III trial that led to registration of the drug a decade ago, there is a substantial increase in the failure rate of oral miltefosine for treatment of VL in India.
authors.affiliation: Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. drshyamsundar@hotmail.com
authors.forename: Shyam
authors.initials: S
authors.lastname: Sundar
authors.forename: Anup
authors.initials: A
authors.lastname: Singh
authors.forename: Madhukar
authors.initials: M
authors.lastname: Rai
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Prajapati
authors.forename: Avinash K
authors.initials: AK
authors.lastname: Singh
authors.forename: Bart
authors.initials: B
authors.lastname: Ostyn
authors.forename: Marleen
authors.initials: M
authors.lastname: Boelaert
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dujardin
authors.forename: Jaya
authors.initials: J
authors.lastname: Chakravarty
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D010767:Phosphorylcholine; C039128:miltefosine