Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients

Vijayamahantesh Vijayamahantesh,Ritesh Mishra,Pradeep Das,Manas R Dikhit,Raj K Pandey,Sanjiva Bimal,V N R Das,Kuljit Singh,Ajay Amit,Henk D F H Schallig

doi:10.1371/journal.pone.0154117

Vijayamahantesh Vijayamahantesh, Ritesh Mishra + Show 8 more

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https://doi.org/10.1371/journal.pone.0154117

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Abstract

Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL.

Highlights

The leishmaniases are protozoan parasite disease caused by more than 20 Leishmania species that are transmitted to humans by the bites of infected sandflies
We found significantly higher ADA level in mononuclear cell lysate in visceral leishmaniasis (VL) pre-treatment stages compared to VL post treatment stages and healthy control (Fig 2A, p0.05)
Active VL cases showed significantly higher ADA activity compared to active PKDL, treated PKDL and healthy control (Fig 2A, p0.05)

Summary

Introduction

The leishmaniases are protozoan parasite disease caused by more than 20 Leishmania species that are transmitted to humans by the bites of infected sandflies. In India, it manifests in 5–15 per cent of VL cases after months or several years of remission from infection, while in Sudan, it develops within weeks or months in 50–60 per cent of cured VL cases [2,3] It is prevalent in the areas where Leishmania donovani is the causative organism [1, 4]. RK39 based test showed sensitivity and specificity estimates of 93.9% and 95.3% respectively[5, 6]. This test has been shown to be less accurate in East Africa [11]. Around 10% of cases have no history of VL, and 10% of cases have no positive serological test making a strict clinical definition important [21]

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Conclusion