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

Dinesh Mondal,Be-Nazir Ahmed,Ridwanur Rahman,Abdul Alim,M Mamun Huda,Moshtaq Mural Ahmed,Abhijit Sharma,Jorge Alvar,Rashidul Haque,Md Golam Hasnain,Amresh Kumar,Jesus G Valenzuela

doi:10.1371/journal.pntd.0007653

Abstract

BackgroundWe investigated the relationship of treatment regimens for visceral leishmaniasis (VL) with post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis relapse (VLR) development.MethodsStudy 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.Findings974 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.InterpretationDevelopment 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.

Highlights

Visceral leishmaniasis (VL) or kala-azar has been a public health problem in Bangladesh over the centuries [1]
There is no strategy for prevention of post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis relapse (VLR)
No study has been carried out to investigate the relationship between treatment regimens for visceral leishmaniasis (VL) and development of PKDL and VLR

Summary

Introduction

Visceral leishmaniasis (VL) or kala-azar has been a public health problem in Bangladesh over the centuries [1]. The epidemiology of VL in Bangladesh, India, and Nepal is similar. In these three countries, the protozoan parasite Leishmania donovani (LD) is the only causative agent of VL, humans are the only reservoir, and the female Phlebotomas argentipes sandfly is the only vector. In 2005, these three countries signed a memorandum of understanding to eliminate VL as a public health problem by 2015, targeting to keep VL incidence less than 1 per 10 000 people at upazila (sub-district), block and district levels in Bangladesh, India and Nepal respectively [3]. Bangladesh and Nepal achieved the target in 2016 and 2013 respectively. We investigated the relationship of treatment regimens for visceral leishmaniasis (VL) with post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis relapse (VLR) development

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