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      Anti-PGL-1 Positivity as a Risk Marker for the Development of Leprosy among Contacts of Leprosy Cases: Systematic Review and Meta-analysis

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          Abstract

          Background

          There is no point of care diagnostic test for infection with M. Leprae or for leprosy, although ELISA anti PGL-1 has been considered and sometimes used as a means to identify infection.

          Methods

          A systematic review of all cohort studies, which classified healthy leprosy contacts, at entry, according to anti-PGL1 positivity, and had at least one year follow up. The outcome was clinical diagnosis of leprosy by an experienced physician. The meta-analysis used a fixed model to estimated OR for the association of PGL-1 positivity and clinical leprosy. A fixed model also estimated the sensibility of PGL-1 positivity and positive predictive value.

          Results

          Contacts who were anti PGL-1 positive at baseline were 3 times as likely to develop leprosy; the proportion of cases of leprosy that were PGL-1 positive at baseline varied but was always under 50%.

          Conclusions

          Although there is a clear and consistent association between positivity to anti PGL-1 and development of leprosy in healthy contacts, selection of contacts for prophylaxis based on anti PGL1 response would miss more than half future leprosy cases. Should chemoprophylaxis of controls be incorporated into leprosy control programmes, PGL1 appears not to be a useful test in the decision of which contacts should receive chemoprophylaxis.

          Author Summary

          Contacts of leprosy cases are more likely to be infected and develop leprosy. But not everyone infected with M. Leprae develops clinical leprosy. into clinical disease. We examined and summarized all the eight studies that evaluated how well PGL-1 predicts which contacts of leprosy will become cases. PGL-1 positive contacts were 3 times more likely to develop leprosy; a variable proportion, but less than 30% of the cases were attributed to PGL-1 and less than 45% of the PGL-1 contacts developed leprosy. PGL1 would not be an appropriate test to decide which contacts of leprosy should receive preventive therapy if this was proposed in leprosy control programmes.

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          Most cited references25

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          Leprosy now: epidemiology, progress, challenges, and research gaps.

          Leprosy continues to be a challenge to health worldwide, with about 250,000 new cases being detected every year. Despite widespread implementation of effective multidrug therapy, leprosy has not been eliminated. A third of newly diagnosed patients have nerve damage and might develop disabilities, although the proportion varies according to several factors, including level of self-care. Women who develop leprosy continue to be especially disadvantaged, with rates of late diagnosis and disability remaining high in this subgroup. Leprosy was not a specified disease in the Millennium Development Goals, but improvements in the other areas they cover, such as education and levels of poverty, will help leprosy patients and services. We review data and make recommendations for research on diagnosis, treatment, and prevention, such as further use of molecular analysis of the Mycobacterium leprae genome, implementation of BCG vaccination, and administration of chemoprophylaxis to household contacts. We also suggest development of tools for early diagnosis and detection of infection and nerve damage, and formulation of strategies to manage the chronic complications of leprosy, such as immune-mediated reactions and neuropathy. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial.

            To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts. Single centre, double blind, cluster randomised, placebo controlled trial. Leprosy control programme in two districts of northwest Bangladesh with a population of more than four million. 28,092 close contacts of 1037 patients with newly diagnosed leprosy. 21,711 contacts fulfilled the study requirements. A single dose of rifampicin or placebo given to close contacts in the second month of starting the index patient's treatment, with follow-up for four years. Development of clinical leprosy. 18,869 of the 21,711 contacts (86.9%) were followed-up at four years. Ninety one of 9452 contacts in the placebo group and 59 of 9417 in the rifampicin group had developed leprosy. The overall reduction in incidence of leprosy using a single dose of rifampicin in the first two years was 57% (95% confidence interval 33% to 72%). The groups did not differ between two and four years. The overall number needed to treat (NNT) to prevent a single case of leprosy among contacts was 297 (95% confidence interval 176 to 537). Differences were found between subgroups at two years, both in reduction of incidence and in NNT. A single dose of rifampicin given to contacts of patients with newly diagnosed leprosy is effective at preventing the development of clinical leprosy at two years. The effect was maintained, but no difference was seen between the placebo and rifampicin groups beyond two years. Current Controlled Trials ISRCTN61223447 [controlled-trials.com].
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              The role of B cells and humoral immunity in Mycobacterium tuberculosis infection.

              Mycobacterium tuberculosis remains a major public health burden. It is generally thought that while B cell- and antibody-mediated immunity plays an important role in host defense against extracellular pathogens, the primary control of intracellular microbes derives from cellular immune mechanisms. Studies on the immune regulatory mechanisms during infection with M. tuberculosis, a facultative intracellular organism, has established the importance of cell-mediated immunity in host defense during tuberculous infection. Emerging evidence suggest a role for B cell and humoral immunity in the control of intracellular pathogens, including obligatory species, through interactions with the cell-mediated immune compartment. Recent studies have shown that B cells and antibodies can significantly impact on the development of immune responses to the tubercle bacillus. In this review, we present experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen. A comprehensive approach that examines both humoral and cellular immunity could lead to better understanding of the immune response to M. tuberculosis.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                18 May 2016
                May 2016
                : 10
                : 5
                : e0004703
                Affiliations
                [1 ]Epidemiology Department, Instituto de Saúde da Comunidade, Universidade Federal Fluminense, Niteroi, Rio de Janeiro, Brasil
                [2 ]Universidade de Brasília, Brasília, DF, Brasil
                [3 ]Universidade Federal de Santa Catarina, Florianópolis, SC, Brasil
                [4 ]Department of Infectious Disease Epidemiology, London School of Hygiene and Public Health, London, England
                University of Tennessee, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MLFP GOP LCR. Performed the experiments: MLFP PCI SN. Analyzed the data: MLFP LCR. Wrote the paper: MLFP LCR GOP PCI SN.

                Article
                PNTD-D-15-01437
                10.1371/journal.pntd.0004703
                4871561
                27192199
                50f22ce9-284d-43f8-a655-ecb3ef2f22f2
                © 2016 Penna et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 August 2015
                : 19 April 2016
                Page count
                Figures: 4, Tables: 4, Pages: 11
                Funding
                Funded by: National Council for Scientific and Technological Development - CNPq-Brazil
                Award ID: 404234/2012-7
                Funded by: CAPES - BRAZIL
                Award ID: 2274-14-0
                This systematic review and meta-analysis was funded by the Department of Science and Technology (DECIT) of Brazilian Ministry of Health and the Brazilian Council for Research (CNPq process 404234/2012-7). MLFP spent a year as a visiting research fellow in London School of Tropical Medicine and Tropical Medicine supported by Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Brazilian Ministry of Education (CAPES process 2274-14-0). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Leprosy
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Leprosy
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Serology
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Research and Analysis Methods
                Research Assessment
                Systematic Reviews
                Biology and Life Sciences
                Organisms
                Bacteria
                Actinobacteria
                Mycobacterium Leprae
                Biology and Life Sciences
                Immunology
                Vaccination and Immunization
                Prophylaxis
                Medicine and Health Sciences
                Immunology
                Vaccination and Immunization
                Prophylaxis
                Medicine and Health Sciences
                Public and Occupational Health
                Preventive Medicine
                Vaccination and Immunization
                Prophylaxis
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Antibodies
                Medicine and Health Sciences
                Physiology
                Immune Physiology
                Antibodies
                Biology and Life Sciences
                Immunology
                Immune System Proteins
                Antibodies
                Medicine and Health Sciences
                Immunology
                Immune System Proteins
                Antibodies
                Biology and Life Sciences
                Biochemistry
                Proteins
                Immune System Proteins
                Antibodies
                Custom metadata
                All data used for analysis are presented in the paper.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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