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      Prospective Study of Leptospirosis Transmission in an Urban Slum Community: Role of Poor Environment in Repeated Exposures to the Leptospira Agent

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          Abstract

          Background

          Leptospirosis has emerged as an urban health problem as slum settlements have rapidly spread worldwide and created conditions for rat-borne transmission. Prospective studies have not been performed to determine the disease burden, identify risk factors for infection and provide information needed to guide interventions in these marginalized communities.

          Methodology/Principal Findings

          We enrolled and followed a cohort of 2,003 residents from a slum community in the city of Salvador, Brazil. Baseline and one-year serosurveys were performed to identify primary and secondary Leptospira infections, defined as respectively, seroconversion and four-fold rise in microscopic agglutination titers. We used multinomial logistic regression models to evaluate risk exposures for acquiring primary and secondary infection. A total of 51 Leptospira infections were identified among 1,585 (79%) participants who completed the one-year follow-up protocol. The crude infection rate was 37.8 per 1,000 person-years. The secondary infection rate was 2.3 times higher than that of primary infection rate (71.7 and 31.1 infections per 1,000 person-years, respectively). Male gender (OR 2.88; 95% CI 1.40–5.91) and lower per capita household income (OR 0.54; 95% CI, 0.30–0.98 for an increase of $1 per person per day) were independent risk factors for primary infection. In contrast, the 15–34 year age group (OR 10.82, 95% CI 1.38–85.08), and proximity of residence to an open sewer (OR 0.95; 0.91–0.99 for an increase of 1 m distance) were significant risk factors for secondary infection.

          Conclusions/Significance

          This study found that slum residents had high risk (>3% per year) for acquiring a Leptospira infection. Re-infection is a frequent event and occurs in regions of slum settlements that are in proximity to open sewers. Effective prevention of leptospirosis will therefore require interventions that address the infrastructure deficiencies that contribute to repeated exposures among slum inhabitants.

          Author Summary

          Leptospirosis is a disease that is transmitted by human contact with an environment contaminated with urine from animals, such as rodents, infected by the Leptospira bacteria. Human illness due to these bacteria can be mild, or can have very severe complications. Residents of urban slum settlements are at high risk for this disease, but the specific risk factors for transmission in these settlements are not understood because of the lack of prospective studies in this epidemiological setting. We performed a prospective study in a Brazilian slum community to measure the risk of infection, identify the environmental and social factors that place slum residents at risk for infection, and determine whether some individuals are at risk of repeated infections. We identified a burden of infection with leptospirosis among slum residents, and found that male gender and low income both increase the risk for infection. In addition, a significant proportion of slum residents had a second exposure to leptospirosis and re-infection occurred most frequently among young adults and the poorest members of the slum community who reside in proximity of open sewers. These risk factors are amenable to interventions aimed to reduce the burden that leptospirosis imparts in this high-risk setting.

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          Most cited references40

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          Leptospira and leptospirosis.

          Leptospirosis is the most wide spread zoonosis worldwide; it is present in all continents except Antarctica and evidence for the carriage of Leptospira has been found in virtually all mammalian species examined. Humans most commonly become infected through occupational, recreational, or domestic contact with the urine of carrier animals, either directly or via contaminated water or soil. Leptospires are thin, helical bacteria classified into at least 12 pathogenic and 4 saprophytic species, with more than 250 pathogenic serovars. Immunity following infection is generally, but not exclusively, mediated by antibody against leptospiral LPS and restricted to antigenically related serovars. Vaccines currently available consist of killed whole cell bacterins which are used widely in animals, but less so in humans. Current work with recombinant protein antigens shows promise for the development of vaccines based on defined protective antigens. The cellular and molecular basis for virulence remains poorly understood, but comparative genomics of pathogenic and saprophytic species suggests that Leptospira expresses unique virulence determinants. However, the recent development of defined mutagenesis systems for Leptospira heralds the potential for gaining a much improved understanding of pathogenesis in leptospirosis. Copyright 2009 Elsevier B.V. All rights reserved.
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            Leptospira: the dawn of the molecular genetics era for an emerging zoonotic pathogen.

            Leptospirosis is a zoonotic disease that has emerged as an important cause of morbidity and mortality among impoverished populations. One hundred years after the discovery of the causative spirochaetal agent, little is understood about Leptospira spp. pathogenesis, which in turn has hampered the development of new intervention strategies to address this neglected disease. However, the recent availability of complete genome sequences for Leptospira spp. and the discovery of genetic tools for their transformation have led to important insights into the biology of these pathogens and their pathogenesis. We discuss the life cycle of the bacterium, the recent advances in our understanding and the implications for the future prevention of leptospirosis.
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              The role of conceptual frameworks in epidemiological analysis: a hierarchical approach.

              This paper discusses appropriate strategies for multivariate data analysis in epidemiological studies. In studies where determinants of disease are sought, it is suggested that the complex hierarchical inter-relationships between these determinants are best managed through the use of conceptual frameworks. Failure to take these aspects into consideration is common in the epidemiological literature and leads to underestimation of the effects of distal determinants. An example of this analytical approach, which is not based purely on statistical associations, is given for assessing determinants of mortality due to diarrhoea in children. Conceptual frameworks provide guidance for the use of multivariate techniques and aid the interpretation of their results in the light of social and biological knowledge.
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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, USA )
                1935-2727
                1935-2735
                May 2014
                29 May 2014
                : 8
                : 5
                : e2927
                Affiliations
                [1 ]Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Saúde, Salvador, Brazil
                [2 ]Escola de Enfermagem, Universidade Federal da Bahia, Salvador, Brazil
                [3 ]Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil
                [4 ]Department of Epidemiology of Microbial Diseases, School of Public Health, Yale University, New Haven, Connecticut, United States of America
                [5 ]Secretaria Estadual de Saúde da Bahia, Salvador, Brazil
                [6 ]Escola Nacional da Saúde Pública, Fundação Oswaldo Cruz, Ministério da Saúde, Rio de Janeiro, Brazil
                [7 ]Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil
                David Geffen School of Medicine at UCLA, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MSC MGR AIK. Performed the experiments: RDMF GSR FC RBR AXTOM DF FSS SM BLdS AQS ACS RRR. Analyzed the data: RDMF GSR JEH FC WST MSC AIK. Contributed reagents/materials/analysis tools: MSC MGR AIK. Wrote the paper: RDMF GSR JEH FC AIK.

                Article
                PNTD-D-14-00081
                10.1371/journal.pntd.0002927
                4038618
                24875389
                c256fadf-ad52-4cc4-940b-06a94927faca
                Copyright @ 2014

                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
                : 17 January 2014
                : 21 April 2014
                Page count
                Pages: 9
                Funding
                This work was supported by the Oswaldo Cruz Foundation and Secretariat of Health Surveillance, Brazilian Ministry of Health; CAPES (Coordination for the Improvement of Higher Education Personnel), Brazilian Ministry of Education; and the National Institutes of Health (grants R01 AI052473, U01 AI088752, R01 TW009504, R24 TW007988, R25 TW009338 and D43 TW00919).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Population Biology
                Veterinary Science
                Veterinary Diseases
                Zoonoses
                Leptospirosis
                Medicine and Health Sciences
                Epidemiology
                Environmental Epidemiology
                Infectious Disease Epidemiology
                Spatial Epidemiology
                Infectious Diseases
                Bacterial Diseases
                Tropical Diseases
                Neglected Tropical Diseases

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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