Leiden University Scholarly Publications

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Hooij, A. van (2021)

Development of immunodiagnostic tests for leprosy: from biomarker discovery to application in endemic areas

Doctoral Thesis
Leprosy is an infectious disease that affects peripheral nerves and can lead to severe lifelong disabilities. Despite the availability of an effective cure, a fairly stable number of about 200,000 new leprosy patients per year has been reported since 2010. This stagnation shows that the transmission of the mycobacteria that cause leprosy, Mycobacterium leprae and Mycobacterium lepromatosis, is still taking place. Timely diagnosis of leprosy patients is therefore vital, so that the time frame in which a person is contagious is shortened, but also irreversible nerve damage and leprosy-associated disabilities can be prevented. However, tools that confirm the diagnosis of leprosy are not yet available. This thesis investigated which factors in blood (the so-called biomarkers) can help to diagnose leprosy. The clinical signs of leprosy have a spectral character and are influenced by the immune response of the host. A combination of biomarkers is described that is able to identify...Show moreLeprosy is an infectious disease that affects peripheral nerves and can lead to severe lifelong disabilities. Despite the availability of an effective cure, a fairly stable number of about 200,000 new leprosy patients per year has been reported since 2010. This stagnation shows that the transmission of the mycobacteria that cause leprosy, Mycobacterium leprae and Mycobacterium lepromatosis, is still taking place. Timely diagnosis of leprosy patients is therefore vital, so that the time frame in which a person is contagious is shortened, but also irreversible nerve damage and leprosy-associated disabilities can be prevented. However, tools that confirm the diagnosis of leprosy are not yet available. This thesis investigated which factors in blood (the so-called biomarkers) can help to diagnose leprosy. The clinical signs of leprosy have a spectral character and are influenced by the immune response of the host. A combination of biomarkers is described that is able to identify patients with a lot of bacteria (multibacillary) as well as the more difficult to diagnose patients with few bacteria (paucibacillary). Subsequently, these biomarkers have been implemented in user-friendly lateral flow assays, which have been extensively validated in leprosy endemic areas.
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Leprosy
Mycobacterium leprae
Up-converting phosphor lateral flow assay
Diagnostic tests
Biomarkers
All authors
Hooij, A. van
Supervisor
Geluk, A.
Co-supervisor
Corstjens, P.L.A.M.
Committee
Helm-van Mil, A.H.M van der; Richardus, J.H.; Rutten, V.P.M.G.; Spencer, J.S.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center [LUMC], Leiden University
Date
2021-11-17

Funding

Sponsorship
The research presented in this thesis was supported by the Netherlands Leprosy Relief Foundation (NLR) and the Leprosy Research Initiative (LRI), both together with the Turing Foundation, The European & Developing Countries Clinical Trials Partnership (EDCTP), the Q.M. Gastmann-Wichers Foundation, the Order of Malta-Grants-for-Leprosy-Research (MALTALEP), the Leiden University Fund (LUF), and the New York Community Trust (NYCT).