Field effectiveness of new visceral leishmaniasis regimens after 1 year following treatment within public health facilities in Bihar, India

PLoS Negl Trop Dis. 2019 Sep 26;13(9):e0007726. doi: 10.1371/journal.pntd.0007726. eCollection 2019 Sep.

Abstract

Background: An earlier open label, prospective, non-randomized, non-comparative, multi-centric study conducted within public health facilities in Bihar, India (CTRI/2012/08/002891) measured the field effectiveness of three new treatment regimens for visceral leishmaniasis (VL): single dose AmBisome (SDA), and combination therapies of AmBisome and miltefosine (AmB+Milt) and miltefosine and paromomycin (Milt+PM) up to 6 months follow-up. The National Vector Borne Disease Control Program (NVBDCP) recommended an extended follow up at 12 months post-treatment of the original study cohort to quantify late relapses.

Methods: The 1,761 patients enrolled in the original study with the three new regimens were contacted and traced between 10 and 36 months following completion of treatment to determine their health status and any occurrence of VL relapse.

Results: Of 1,761 patients enrolled in the original study, 1,368 were traced at the extended follow-up visit: 711 (80.5%), 295 (83.2%) and 362 (71.5%) patients treated with SDA, AmB+Milt and Milt+PM respectively. Of those traced, a total of 75 patients were reported to have relapsed by the extended follow-up; 45 (6.3%) in the SDA, 25 (8.5%) in the AmB+Milt and 5 (1.4%) in the Milt+PM arms. Of the 75 relapse cases, 55 had already been identified in the 6-months follow-up and 20 were identified as new cases of relapse at extended follow-up; 7 in the SDA, 10 in the AmB+Milt and 3 in the Milt+PM arms.

Conclusion: Extending follow-up beyond the standard 6 months identified additional relapses, suggesting that 12-month sentinel follow-up may be useful as a programmatic tool to better identify and quantify relapses. With limited drug options, there remains an urgent need to develop effective new chemical entities (NCEs) for VL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amphotericin B / therapeutic use
  • Antiprotozoal Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • India
  • Leishmaniasis, Visceral / drug therapy*
  • Male
  • Paromomycin / therapeutic use
  • Phosphorylcholine / analogs & derivatives
  • Phosphorylcholine / therapeutic use
  • Recurrence
  • Treatment Outcome

Substances

  • Antiprotozoal Agents
  • liposomal amphotericin B
  • Phosphorylcholine
  • miltefosine
  • Paromomycin
  • Amphotericin B

Grants and funding

This study was funded by the Bill & Melinda Gates Foundation, USA (Grant Number OPP1017832) and the Dutch Ministry of Foreign Affairs (DGIS), the Netherlands. For its overall mission, DNDi receives financial support from UK aid, UK; Médecins sans Frontières (MSF), International and the Swiss Agency for Development and Cooperation (SDC), Switzerland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.