Long-term incidence of relapse and post-kala-azar dermal leishmaniasis after three different visceral leishmaniasis treatment regimens in Bihar, India

PLoS Negl Trop Dis. 2020 Jul 20;14(7):e0008429. doi: 10.1371/journal.pntd.0008429. eCollection 2020 Jul.

Abstract

Background: Few prospective data exist on incidence of post kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis (VL) relapse after different treatment regimens.

Methodology/principal findings: A Phase IV trial included 1761 VL patients treated between 2012-2014 with single dose AmBisome (SDA; N = 891), miltefosine-paromomycin (Milt-PM; n = 512), or AmBisome-miltefosine (AmB-Milt; n = 358). Follow-up for PKDL and VL relapse was scheduled for 6, 12 and 24 months after treatment, lasting until 2017. Patients with lesions consistent with PKDL were tested by rK39 rapid test, and if positive, underwent skin-snip sampling, smear microscopy and PCR. Probable PKDL was defined by consistent lesions and positive rK39; confirmed PKDL required additional positive microscopy or PCR. PKDL and relapse incidence density were calculated by VL treatment and risk factors evaluated in Cox proportional hazards models. Among 1,750 patients who completed treatment, 79 had relapse and 104 PKDL. Relapse incidence density was 1.58, 2.08 and 0.40 per 1000 person-months for SDA, AmB-Milt and Milt-PM, respectively. PKDL incidence density was 1.29, 1.45 and 2.65 per 1000 person-months for SDA, AmB-Milt and Milt-PM. In multivariable models, patients treated with Milt-PM had lower relapse but higher PKDL incidence than those treated with SDA; AmB-Milt rates were not significantly different from those for SDA. Children <12 years were at higher risk for both outcomes; females had a higher risk of PKDL but not relapse.

Conclusions/significance: Active surveillance for PKDL and relapse, followed by timely treatment, is essential to sustain the achievements of VL elimination programs in the Indian sub-continent.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amphotericin B / administration & dosage*
  • Antiprotozoal Agents / administration & dosage*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Humans
  • Incidence
  • India / epidemiology
  • Leishmaniasis, Cutaneous / parasitology*
  • Leishmaniasis, Cutaneous / pathology
  • Leishmaniasis, Visceral / drug therapy*
  • Leishmaniasis, Visceral / parasitology
  • Male
  • Middle Aged
  • Prospective Studies
  • Recurrence
  • Young Adult

Substances

  • Antiprotozoal Agents
  • liposomal amphotericin B
  • Amphotericin B

Grants and funding

This study was funded by the Bill & Melinda Gates Foundation, USA (Grant Number OPP1017832); the Dutch Ministry of Foreign Affairs (DGIS), the Netherlands; the French Development Agency (AFD), France; and the World Health Organization-Special Programme for Research and Training in Tropical Diseases (WHO-TDR). 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.