Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy

Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis

Comparing the Clinical and Histological Diagnosis of Leprosy and Leprosy Reactions in the INFIR Cohort of Indian Patients with Multibacillary Leprosy

Leprosy affects skin and peripheral nerves. Although we have antibiotics to treat the mycobacterial infection, the accompanying inflammation is a major part of the disease process. This can worsen after starting antibacterial treatment with episodes of immune mediated inflammation, so called reactions. These are associated with worsening of nerve damage. However, diagnosing these reactions is not straightforward. They can be diagnosed clinically by examination or by microscopic examination of the skin biopsies. We studied a cohort of 303 newly diagnosed leprosy patients in India and compared the diagnosis rates by clinical examination and microscopy and found that the microscopic diagnosis has higher rates of diagnosis for both types of reaction. This suggests that clinicians and pathologists have different thresholds for diagnosing reactions. More work is needed to optimise both clinical and pathological diagnosis. In this cohort 43% of patients had Borderline Tuberculoid leprosy, an immunologically active type, and 20% of the biopsies showed only minimal inflammation, perhaps these patients had very early disease or self-healing. The public health implication of this work is that leprosy centres need to be supported by pathologists to help with the clinical management of difficult cases

Inkomen verdeeld, trends 1977-2019

bookHervorming Sociale Regelgevin

Inkomens verdeeld, 40 jaar in vogelvlucht

Deze publicatie is een samenvatting van het boek Inkomen verdeeld, trends 1977-2019. Beschikbaar via https://hdl.handle.net/1887/3216933Hervorming Sociale Regelgevin

Detection of anti-M. leprae antibodies in children in leprosy-endemic areas: a systematic review

Background Leprosy elimination primarily targets transmission of Mycobacterium leprae which is not restricted to patients' households. As interruption of transmission is imminent in many countries, a test to detect infected asymptomatic individuals who can perpetuate transmission is required. Antibodies directed against M. leprae antigens are indicative of M. leprae infection but cannot discriminate between active and past infection. Seroprevalence in young children, however, reflects recent M. leprae infection and may thus be used to monitor transmission in an area. Therefore, this literature review aimed to evaluate what has been reported on serological tests measuring anti-M. leprae antibodies in children without leprosy below the age of 15 in leprosy-endemic areas. Methods and findings A literature search was performed in the databases Pubmed, Infolep, Web of Science and The Virtual Health Library. From the 724 articles identified through the search criteria, 28 full-text articles fulfilled all inclusion criteria. Two additional papers were identified through snowballing, resulting in a total of 30 articles reporting data from ten countries. All serological tests measured antibodies against phenolic glycolipid-I or synthetic derivatives thereof, either quantitatively (ELISA or UCP-LFA) or qualitatively (ML-flow or NDO-LID rapid test). The median seroprevalence in children in endemic areas was 14.9% and was stable over time if disease incidence remained unchanged. Importantly, seroprevalence decreased with age, indicating that children are a suitable group for sensitive assessment of recent M. leprae infection. However, direct comparison between areas, solely based on the data reported in these studies, was impeded by the use of different tests and variable cut-off levels. Conclusions Quantitative anti-PGL-I serology in young children holds promise as a screening test to assess M. leprae infection and may be applied as a proxy for transmission and thereby as a means to monitor the effect of (prophylactic) interventions on the route to leprosy elimination.Author summary Leprosy, a chronic infectious disease caused by Mycobacterium leprae (M. leprae), targets the skin and nerves and often results in irreversible disabilities as well as social exclusion. Though the disease can be efficiently treated, leprosy elimination is hampered by ongoing transmission of M. leprae. Currently, elimination is monitored by the number of new cases. Since only a small percentage of individuals infected with M. leprae develops disease, this does not accommodate monitoring of transmission. Previous studies have shown that antibody levels against M. leprae in blood correspond to the bacterial load in an individual and can be used as a proxy for infection, although antibodies cannot distinguish between past and present infection. In young children, infection is recent by definition, which allows assessment of more current state of transmission in an area. Thus, this literature review investigated studies on leprosy serology in children without leprosy. Our findings underscore that young children are a fitting group for up-to-date monitoring of M. leprae transmission in an area as seropositivity is inversely related with age. Importantly, a standardized, field-friendly test quantitatively measuring anti-M. leprae antibodies should be applied for population screening to monitor the status of transmission and thereby elimination in an area.Immunogenetics and cellular immunology of bacterial infectious disease

Leprosy Post-Exposure Prophylaxis (LPEP) Programme : study protocol for evaluating the feasibility and impact on case detection rates of contact tracing and single dose rifampicin

Introduction: The reported number of new leprosy patients has barely changed in recent years. Thus, additional approaches or modifications to the current standard of passive case detection are needed to interrupt leprosy transmission. Large-scale clinical trials with single dose rifampicin (SDR) given as post-exposure prophylaxis (PEP) to contacts of newly diagnosed patients with leprosy have shown a 50–60% reduction of the risk of developing leprosy over the following 2 years. To accelerate the uptake of this evidence and introduction of PEP into national leprosy programmes, data on the effectiveness, impact and feasibility of contact tracing and PEP for leprosy are required. The leprosy post-exposure prophylaxis (LPEP) programme was designed to obtain those data. Methods and analysis: The LPEP programme evaluates feasibility, effectiveness and impact of PEP with SDR in pilot areas situated in several leprosy endemic countries: India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Complementary sites are located in Brazil and Cambodia. From 2015 to 2018, contact persons of patients with leprosy are traced, screened for symptoms and assessed for eligibility to receive SDR. The intervention is implemented by the national leprosy programmes, tailored to local conditions and capacities, and relying on available human and material resources. It is coordinated on the ground with the help of the in-country partners of the International Federation of Anti-Leprosy Associations (ILEP). A robust data collection and reporting system is established in the pilot areas with regular monitoring and quality control, contributing to the strengthening of the national surveillance systems to become more action-oriented. Ethics and dissemination: Ethical approval has been obtained from the relevant ethics committees in the countries. Results and lessons learnt from the LPEP programme will be published in peer-reviewed journals and should provide important evidence and guidance for national and global policymakers to strengthen current leprosy elimination strategies

Cytokine and Protein Markers of Leprosy Reactions in Skin and Nerves: Baseline Results for the North Indian INFIR Cohort

Leprosy affects skin and peripheral nerves. Although we have effective antibiotics to treat the mycobacterial infection, a key part of the disease process is the accompanying inflammation. This can worsen after starting antibacterial treatment with episodes of immune mediated inflammation, so called ‘reactions’. These reactions are associated with worsening of the nerve damage. We recruited a cohort of 303 newly diagnosed leprosy patients in North India with the aim of understanding and defining the pathological processes better. We took skin and nerve biopsies from patients and examined them to define which molecules and mediators of inflammation were present. We found high levels of the cytokines Tumour Necrosis Factor alpha, Transforming Growth Factor beta and inducible Nitric Oxide Synthase in biopsies from patients with reactions. We also found high levels of bacteria and inflammation in the nerves. These experiments tell us that we need to determine which other molecules are present and to explore ways of switching off the production of these pro-inflammatory molecules

Macrophage Depletion in Hypertensive Rats Accelerates Development of Cardiomyopathy

Inflammation contributes to the process of ventricular remodeling after acute myocardial injury. To investigate the role of macrophages in the chronic process of cardiac remodeling, they were selectively depleted by intravenous administration of liposomal clodronate in heart failure-prone hypertensive Ren-2 rats from the age of 7 until 13 weeks. plain liposomes were used for comparison. Liposomal clodronate treatment reduced the number of blood monocytes and decreased the number of macrophages in the myocardium. Compared to plain liposomes, liposomal clodronate treatment rapidly worsened left ventricular ejection function in hypertensive rats. Liposomal clodronate-treated Ren-2 rat hearts showed areas of myocyte loss with abundant inflammatory cell infiltration, predominantly comprising CD4 positive T lymphocytes. The current-study showed that lack of macrophages vas associated with earlier development of myocardial dysfunction in hypertensive rats. Modulation of macrophage function may be of value in the evolution of cardiomyopath