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Name: Ismail, Ahmed
Home country: Sudan
Research country: Sudan
Project period: 1997-2000
Title
Immune responses and immunopathology of post kala-azar dermal leishmaniasis (PKDL)
Abstract
Background and Objectives
Post kala-azar dermal leishmaniasis (PKDL) is a known complication of visceral leishmaniasis (VL), which can lead to severe disfigurement of affected patient. It is characterised by skin lesions that follow apparently successful treatment of VL. In a minority of patients PKDL develops without anteceded VL. Lesions may be macules, papules, nodules or a combination of these. Lesions are characterised by presence of scanty parasites. They can be confused with other skin diseases in particular leprosy. PKDL is almost confined to the Indian subcontinent and East Africa and is considered as an important reservoir for the disease in some areas. Seventy years had passed since the report of the first case in India, but the pathogenesis is still obscure and it is a puzzle why a severe systemic infection characteristic of kala-azar is followed by skin symptoms after apparently successful drug treatment. It was suggested that insufficient or inappropriate immune response in the skin could play a role in the pathogenesis of the disease.
Based on the above background and in order to clarify the pathogenesis of PKDL the objectives of this thesis were:
(1) To characterise the immune response in the peripheral blood and in the lesions of patients with active PKDL.
(2) To characterise the parasite causing the disease.
(3) To develop and evaluate a reliable and sensitive laboratory test for the diagnosis of PKDL.
The outline of the thesis
This thesis consists of five chapters:
- Chapter I: As an introduction the first chapter gives an overview of leishmaniasis focussing on visceral leishmaniasis, Leishmania parasites the causative agent of the disease and immunology of leishmaniasis. This chapter also includes a comprehensive section on literature review on post kala-azar dermal leishmaniasis.
- Chapter II: Deals with the methodologies used and the results obtained
2.1. By using irnmunohistochemistry technique and specific monoclonal antibody against L. donovani the parasite causing PKDL was characterised. The method is sensitive and specific for the detection of parasites or parasite antigen in lesions that have scanty parasites in sections stained with haematoxylin and eosin.
2.2. This section describes the pathology of lesions and draining lymph nodes from patients with active PKDL by fight microscopy, immunohistochemistry and electron microscopy.
2.3. Cell-mediated immune response in peripheral blood mononuclear cells (PBMC) by in vivo and in vitro study and cytokine profile in dermal lesions were studied in this section.
2.4. Based on clinical observation on patients with PKDL which showed that the lesion confined to or more severe in sun-exposed parts of the skin, it was hypothesise, ultraviolet (UVB) light could play a role in the pathogenesis of the disease. In this section immunohistochemical evidence which is consistent with this hypothesis is provided.
- Chapter III: lncludes overall discussion and conclusions
- Chapter IV: Further studies
Involved research institutions
Centre for Medical Parasitology, University of Copenhagen
Supervisor(s)
Thor Theander, Centre for Medical Parasitology, University of Copenhagen
Correspondence
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