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

Allen Hightower,Shambhu Nath Singh,Suman Rijal,Ravi Shankar Singh,Krishna Pandey,Vidya Nand Rabi Das,Fabiana Alves,Caryn Bern,Guilherme L. Werneck,Jorge Alvar,Vishal Goyal,Pradeep Das,Neena Verma

doi:10.1371/journal.pntd.0008429

Abstract

BackgroundFew prospective data exist on incidence of post kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis (VL) relapse after different treatment regimens.Methodology/Principal findingsA 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/SignificanceActive surveillance for PKDL and relapse, followed by timely treatment, is essential to sustain the achievements of VL elimination programs in the Indian sub-continent.

Highlights

India has seen an unprecedented decrease in visceral leishmaniasis (VL) incidence over the past decade, with yearly case numbers lower than at any time since the 1970s [1]
Efforts to eliminate visceral leishmaniasis (VL) in the Indian subcontinent have had an unprecedented impact on the number of cases over the past decade, the disease is known to be cyclical and previous periods of low incidence have been followed by a major resurgence
The disease is thought to be maintained between epidemics as postkala-azar dermal leishmaniasis (PKDL), a skin disease affecting 5 to 15% of apparently cured VL patients in the Indian subcontinent

Summary

Introduction

India has seen an unprecedented decrease in visceral leishmaniasis (VL) incidence over the past decade, with yearly case numbers lower than at any time since the 1970s [1]. This success resulted, at least in part, from the concerted efforts within the kala-azar elimination programme to decrease diagnostic delays and provide effective treatment for VL patients, and integrated vector control. Post-kala-azar dermal leishmaniasis (PKDL) has long been postulated to act as the major inter-epidemic reservoir [5]. Few prospective data exist on incidence of post kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis (VL) relapse after different treatment regimens

Methods

Results

Discussion

Conclusion