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... 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. Show less
Leprosy is a multifactorial chronic disease caused by Mycobacterium leprae or Mycobacterium lepromatosis that affects the skin and nerves. More than 200.000 new cases are diagnosed per year; thus,... Show moreLeprosy is a multifactorial chronic disease caused by Mycobacterium leprae or Mycobacterium lepromatosis that affects the skin and nerves. More than 200.000 new cases are diagnosed per year; thus, transmission is still ongoing. The most likely way of transmission is the respiratory route form human-to-human; however, transmission is still not clearly understood. Early diagnosis of leprosy is crucial to reduce and avoid transmission as well as leprosy-associated disabilities, which are also a cause of stigma. Currently, diagnosis is performed based on clinical signs and symptoms and late- or mis-diagnosis are not uncommon.In this thesis, we combined the study of pathogen transmission with host transcriptomic and genomic biomarkers. To explore M. leprae transmission a One Health approach was followed, where human, animal and environmental samples were studied.The combination of demographic characteristics, pathogen detection, genetic and/or transcriptomic biomarkers can be applied in a multifactorial leprosy signature applicable for early diagnosis of leprosy and/or to guide intervention strategies. Identification of predictive biomarkers will in due course lead to prompt treatment, preventing leprosy-associated irreversible disabilities as well as reducing M. leprae transmission. Show less
Mycobacterium leprae, the causative agent of leprosy, is still actively transmitted in endemic areas reflected by the fairly stable number of new cases detected each year. Recognizing the signs and... Show moreMycobacterium leprae, the causative agent of leprosy, is still actively transmitted in endemic areas reflected by the fairly stable number of new cases detected each year. Recognizing the signs and symptoms of leprosy is challenging, especially at an early stage. Improved diagnostic tools, based on sensitive and specific biomarkers, that facilitate diagnosis of leprosy are therefore urgently needed. In this review, we address the challenges that leprosy biomarker research is facing by reviewing cell types reported to be involved in host immunity to M leprae. These cell types can be associated with different possible fates of M leprae infection being either protective immunity, or pathogenic immune responses inducing nerve damage. Unraveling these responses will facilitate the search for biomarkers. Implications for further studies to disentangle the complex interplay between host responses that lead to leprosy disease are discussed, providing leads for the identification of new biomarkers to improve leprosy diagnostics. Show less
