Relationship between treatment regimens for visceral leishmaniasis and development of post-kala-azar dermal leishmaniasis and visceral leishmaniasis relapse: A cohort study from Bangladesh

PLoS Negl Trop Dis. 2019 Aug 15;13(8):e0007653. doi: 10.1371/journal.pntd.0007653. eCollection 2019 Aug.


Background: We investigated the relationship of treatment regimens for visceral leishmaniasis (VL) with post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis relapse (VLR) development.

Methods: Study subjects included cohorts of patients cured of VL since treatment with monotherapy by sodium stibogluconate (SSG), miltefosine (MF), paromomycin intramuscular injection (PMIM), liposomal amphotericin B [AmBisome (AMB)] in a single dose (SDAMB) and in multidose (MDAMB), and combination therapies by AMB+PMIM, AMB+MF, and PMIM+MF. Follow up period was 4 years after treatment. Cohorts were prospective except SSG (retrospective) and MF (partially retrospective). We compared incidence proportion and rate in 100-person-4year of PKDL and VLR by treatment regimens using univariate and multivariate analysis.

Findings: 974 of 984 enrolled participants completed the study. Overall incidence proportion for PKDL and VLR was 12.3% (95% CI, 10.4%-14.5%) and 7.0% (95% CI, 5.6%-8.8%) respectively. The incidence rate (95% CI) of PKDL and VLR was 14.0 (8.6-22.7) and 7.6 (4.1-14.7) accordingly. SSG cohort had the lowest incidence rate of PKDL at 3.0 (1.3-7.3) and VLR at 1.8 (0.6-5.6), followed by MDAMB at 8.2 (4.3-15.7) for PKDL and at 2.7 (0.9-8.4) for VLR.

Interpretation: Development of PKDL and VLR is related with treatment regimens for VL. SSG and MDAMB resulted in less incidence of PKDL and VLR compared to other treatment regimens. MDAMB should be considered for VL as a first step for prevention of PKDL and VLR since SSG is highly toxic and not recommended for VL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiprotozoal Agents / therapeutic use*
  • Bangladesh / epidemiology
  • Drug Therapy / methods*
  • Drug Therapy, Combination / methods
  • Female
  • Humans
  • Incidence
  • Injections, Intramuscular
  • Leishmaniasis, Cutaneous / epidemiology*
  • Leishmaniasis, Visceral / complications*
  • Leishmaniasis, Visceral / drug therapy*
  • Male
  • Middle Aged
  • Prospective Studies
  • Recurrence
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult


  • Antiprotozoal Agents

Grants and funding

This study was funded by the Bill & Melinda Gates Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.