title: Five-year field results and long-term effectiveness of 20 mg/kg liposomal amphotericin B (Ambisome) for visceral leishmaniasis in Bihar, India.
abstract: BACKGROUND
  Visceral Leishmaniasis (VL; also known as Kala-azar) is an ultimately fatal disease endemic in Bihar. A 2007 observational cohort study in Bihar of 251 patients with VL treated with 20 mg/Kg intravenous liposomal amphotericin B (Ambisome) demonstrated a 98% cure rate at 6-months. Between July 2007 and August 2012, Médecins Sans Frontières (MSF) and the Rajendra Memorial Research Institute (RMRI) implemented a VL treatment project in Bihar, India-an area highly endemic for Leishmania donovani-using this regimen as first-line treatment.
  
  
  RESULTS
  Intravenous Ambisome 20 mg/kg was administered in four doses of 5 mg/kg over 4-10 days, depending on the severity of disease. Initial clinical cure at discharge was defined as improved symptoms, cessation of fever, and recession of spleen enlargement. This observational retrospective cohort study describes 8749 patients with laboratory-confirmed primary VL treated over a 5-year period: 1396 at primary healthcare centers, 7189 at hospital, and 164 at treatment camps. Initial clinical cure was achieved in 99.3% of patients (8692/8749); 0.3% of patients (26/8749) defaulted from treatment and 0.4% (31/8749) died. Overall, 1.8% of patients (161/8749) were co-infected with HIV and 0.6% (51/8749) with tuberculosis. Treatment was discontinued because of severe allergic reactions in 0.1% of patients (7/8749). Overall, 27 patients (0.3%) were readmitted with post Kala-azar dermal leishmaniasis (PKDL). Risk factors for late presentation included female sex, age >15 years and being from a scheduled caste. In 2012, a long-term efficacy survey in the same area of Bihar determined relapse rates of VL after 5 years' intervention with Ambisome. Of 984 immunocompetent patients discharged between September 2010 and December 2011, 827 (84.0%) were traced in order to determine their long-term outcomes. Of these, 20 patients (2.4%) had relapsed or received further treatment for VL. Of those completing 6, 12, and 15 month follow-up, 0.3% (2/767), 3.7% (14/383), and 2.4% (4/164), respectively, had relapsed. The mean ±SD time-to-relapse was 9.6±3.0 months.
  
  
  CONCLUSIONS
  This is the largest cohort of VL patients treated with 20 mg/kg Ambisome worldwide. The drug has high initial and long-term efficacy, and a low rate of adverse reactions when administered under field conditions in Bihar, India. Although challenging, its use as first line treatment in rural settings in Bihar is safe and feasible.
authors.affiliation: Médecins Sans Frontières, New Delhi, India.
authors.forename: Sakib
authors.initials: S
authors.lastname: Burza
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences, Patna, Bihar, India.
authors.forename: Prabhat K
authors.initials: PK
authors.lastname: Sinha
authors.affiliation: Médecins Sans Frontières, New Delhi, India.
authors.forename: Raman
authors.initials: R
authors.lastname: Mahajan
authors.affiliation: Médecins Sans Frontières, Barcelona, Spain.
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Lima
authors.affiliation: Médecins Sans Frontières, New Delhi, India.
authors.forename: Gaurab
authors.initials: G
authors.lastname: Mitra
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences, Patna, Bihar, India.
authors.forename: Neena
authors.initials: N
authors.lastname: Verma
authors.forename: Manica
authors.initials: M
authors.lastname: Balasegaram
authors.affiliation: ACCESS Campaign, Geneva, Switzerland.
authors.forename: Manica
authors.initials: M
authors.lastname: Balasegarem
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences, Patna, Bihar, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Das
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007194:India; D007223:Infant; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C068538:liposomal amphotericin B; D000666:Amphotericin B