Abstract

BackgroundIn areas endemic for visceral leishmaniasis (VL), a large number of infected individuals mount a protective cellular immune response and remain asymptomatic carriers. We propose an interferon-gamma release assay (IFN-γRA) as a novel marker for latent L. donovani infection.Methods and FindingsWe modified a commercial kit (QuantiFERON) evaluating five different leishmania-specific antigens; H2B, H2B-PSA2, H2B-Lepp12, crude soluble antigen (CSA) and soluble leishmania antigen (SLA) from L. donovani with the aim to detect the cell-mediated immune response in VL. We evaluated the assay on venous blood samples of active VL patients (n = 13), cured VL patients (n = 15), non-endemic healthy controls (n = 11) and healthy endemic controls (n = 19). The assay based on SLA had a sensitivity of 80% (95% CI = 54.81–92.95) and specificity of 100% (95% CI = 74.12–100).ConclusionOur findings suggest that a whole-blood SLA-based QuantiFERON assay can be used to measure the cell-mediated immune response in L. donovani infection. The positive IFN-γ response to stimulation with leishmania antigen in patients with active VL was contradictory to the conventional finding of a non-proliferative antigen-specific response of peripheral blood mononuclear cells and needs further research.

Highlights

  • Visceral leishmaniasis (VL) known as kala-azar is the most severe form of leishmaniasis and is a chronic systemic disease that is fatal unless treated

  • Our findings suggest that a whole-blood soluble leishmania antigen (SLA)-based QuantiFERON assay can be used to measure the cellmediated immune response in L. donovani infection

  • The positive IFN-c response to stimulation with leishmania antigen in patients with active visceral leishmaniasis (VL) was contradictory to the conventional finding of a non-proliferative antigen-specific response of peripheral blood mononuclear cells and needs further research

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Summary

Introduction

Visceral leishmaniasis (VL) known as kala-azar is the most severe form of leishmaniasis and is a chronic systemic disease that is fatal unless treated. In 2005 the governments of India and Bangladesh embarked on a VL elimination program with the goal to reduce the incidence of disease below 1 per 10 000 per year (TDR 2005). The asymptomatic L.donovani carriers usually outnumber the number of clinical cases, with ratios varying between 4 to 1 in Bangladesh [4] and 10 to 1 in India and Nepal [5]. For the VL elimination initiative it will be critical though to document the trends in incident L.donovani infections in the few years. Serologic testing is generally assumed to detect more recent infection, but the length of time for which serology remains positive, and whether this differs between kala azar patients and asymptomatically infected individuals (as seems likely based on the magnitude of the titers), is not known with certainty. We propose an interferon-gamma release assay (IFN-cRA) as a novel marker for latent L. donovani infection

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