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Owen, Sophie 
ORCID: https://orcid.org/0000-0002-0458-2357
(2022)
Development and evaluation of diagnostics for visceral leishmaniasis focussing on people living with HIV and asymptomatic infections, Thesis (Doctoral), Liverpool School of Tropical Medicine.
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Abstract
The Indian subcontinent (ISC) was targeting visceral leishmaniasis (VL) for elimination by 2020, with Bihar, an endemic state in India a major focus of the campaign. Current diagnostics for VL such as the direct agglutination test (DAT) and rK39 tests detect antibodies, making it difficult to distinguish between past or current infection, particularly in the absence of clinical symptoms or typical VL. Asymptomatic Leishmania infections (ALI) outnumber symptomatic infections on the ISC and people living with human immunodeficiency virus (PLHIV) have a higher risk of developing symptoms of VL with high treatment failure, relapse, and mortality, presenting a major challenge for both clinical management and elimination. PLHIV and asymptomatic individuals are of importance to VL elimination, particularly where the reservoir host is thought to be anthroponotic. Diagnostics that enable the detection of ALI, diagnosis of acute VL and Leishmania-HIV co-infections, monitoring VL treatment, and surveillance are needed. The Leishmania antigen enzyme-linked immunosorbent assay (ELISA) (Clin-Tech, UK) measures antigenuria, therefore identifying antigens excreted in urine during current infections, potentially allowing monitoring of VL treatment response, and predicting treatment failure and relapse in PLHIV. Testing urine is non-invasive and has the potential to replace invasive tissue aspiration. Real-time polymerase chain reaction (qPCR) is a highly sensitive technique to detect Leishmania donovani (L. donovani) kinetoplast DNA (kDNA). Similarly, loop-mediated isothermal amplification (LAMP) is a technique used to amplify DNA suitable for resource-poor settings. However, the clinical utility of the Leishmania antigen ELISA and molecular techniques in asymptomatic and symptomatic L. donovani infections with and without HIV has not been fully established in an elimination setting. In this thesis, I describe the prevalence and determinants of ALI, and the utility and diagnostic accuracy of the Leishmania antigen ELISA, DAT, LAMP, and qPCR for the detection of ALI in a cohort of 720 contacts of people with VL and PKDL in Bangladesh (chapter 2). Further, I describe the prevalence and determinants of ALI, and examine the utility of the Leishmania antigen ELISA, qPCR, rK39 rapid diagnostic test (RDT), and rK39 ELISA for the detection of ALI in a cohort of 1,300 PLHIV in India (chapter 3). The latter cohort were followed for 18 months to evaluate the rate and risk factors for disease progression from ALI to VL in PLHIV and to determine the utility of the Leishmania antigen ELISA, qPCR, rK39 RDT, and rK39 ELISA as markers of progression (chapter 4). I then describe the potential use of these assays as diagnostic and test of cure assays for VL in a cohort of HIV co-infected patients in India (chapter 5). In a final chapter, I screened a panel of thirteen monoclonal antibodies for the development of an alternative antigen detection test and evaluated other available antigen detection assays (chapter 6).
| Item Type: | Thesis (Doctoral) | ||||
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| Subjects: | WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.5 Complications WC Communicable Diseases > Tropical and Parasitic Diseases > WC 680 Tropical diseases (General) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 715 Visceral leishmaniasis |
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| Faculty: Department: | Biological Sciences > Department of Tropical Disease Biology | ||||
| Depositing User: | Lynn Roberts-Maloney | ||||
| Date Deposited: | 27 Sep 2022 13:13 | ||||
| Last Modified: | 27 Dec 2022 02:02 | ||||
| URI: | https://archive.lstmed.ac.uk/id/eprint/21216 |
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