title: Risk factors for visceral leishmaniasis relapse in immunocompetent patients following treatment with 20 mg/kg liposomal amphotericin B (Ambisome) in Bihar, India.
abstract: BACKGROUND
  A proportion of all immunocompetent patients treated for visceral leishmaniasis (VL) are known to relapse; however, the risk factors for relapse are not well understood. With the support of the Rajendra Memorial Research Institute (RMRI), Médecins Sans Frontières (MSF) implemented a program in Bihar, India, using intravenous liposomal amphotericin B (Ambisome) as a first-line treatment for VL. The aim of this study was to identify risk factors for VL relapse by examining the characteristics of immunocompetent patients who relapsed following this regimen.
  
  
  RESULTS
  This is an observational retrospective cohort study of all VL patients treated by the MSF program from July 2007 to August 2012. Intravenous Ambisome was administered to 8749 patients with VL in four doses of 5 mg/kg (for a total dose of 20 mg/kg) over 4-10 days, depending on the severity of disease. Out of 8588 patients not known to be HIV-positive, 8537 (99.4%) were discharged as initial cures, 24 (0.3%) defaulted, and 27 (0.3%) died during or immediately after treatment. In total, 1.4% (n = 119) of the initial cured patients re-attended the programme with parasitologically confirmed VL relapse, with a median time to relapse of 10.1 months. Male sex, age <5 years and ≥45 years, a decrease in spleen size at time of discharge of ≤0.5 cm/day, and a shorter duration of symptoms prior to seeking treatment were significantly associated with relapse. Spleen size at admission, hemoglobin level, nutritional status, and previous history of relapse were not associated with relapse.
  
  
  CONCLUSIONS
  This is the largest cohort of VL patients treated with Ambisome worldwide. The risk factors for relapse included male sex, age <5 and ≥45 years, a smaller decrease in splenomegaly at discharge, and a shorter duration of symptoms prior to seeking treatment. The majority of relapses in this cohort occurred 6-12 months following treatment, suggesting that a 1-year follow-up is appropriate in future studies.
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: Balsegaram
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*; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000453:epidemiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000981:Antiprotozoal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B