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      Leptospirosis in Rio Grande do Sul, Brazil: An Ecosystem Approach in the Animal-Human Interface

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          Abstract

          Background

          Leptospirosis is an epidemic-prone neglected disease that affects humans and animals, mostly in vulnerable populations. The One Health approach is a recommended strategy to identify drivers of the disease and plan for its prevention and control. In that context, the aim of this study was to analyze the distribution of human cases of leptospirosis in the State of Rio Grande do Sul, Brazil, and to explore possible drivers. Additionally, it sought to provide further evidence to support interventions and to identify hypotheses for new research at the human-animal-ecosystem interface.

          Methodology and findings

          The risk for human infection was described in relation to environmental, socioeconomic, and livestock variables. This ecological study used aggregated data by municipality (all 496). Data were extracted from secondary, publicly available sources. Thematic maps were constructed and univariate analysis performed for all variables. Negative binomial regression was used for multivariable statistical analysis of leptospirosis cases. An annual average of 428 human cases of leptospirosis was reported in the state from 2008 to 2012. The cumulative incidence in rural populations was eight times higher than in urban populations. Variables significantly associated with leptospirosis cases in the final model were: Parana/Paraiba ecoregion (RR: 2.25; CI 95%: 2.03–2.49); Neossolo Litolítico soil (RR: 1.93; CI 95%: 1.26–2.96); and, to a lesser extent, the production of tobacco (RR: 1.10; CI 95%: 1.09–1.11) and rice (RR: 1.003; CI 95%: 1.002–1.04).

          Conclusion

          Urban cases were concentrated in the capital and rural cases in a specific ecoregion. The major drivers identified in this study were related to environmental and production processes that are permanent features of the state. This study contributes to the basic knowledge on leptospirosis distribution and drivers in the state and encourages a comprehensive approach to address the disease in the animal-human-ecosystem interface.

          Author Summary

          Leptospirosis is a bacterial disease affecting humans and several animal species, which serve as reservoirs for infection. Contamination happens through exposure to urine of infected animals in water and soil.

          A better understanding of the factors that affect the transmission of the disease, incorporating the relationship between humans, animals, and ecosystems within the One Health approach, would allow for tailored prevention and control measures at the local level. The aims of this study were to analyze the distribution of leptospirosis human cases and the possible factors that influence the transmission of the disease in the state of Rio Grande do Sul, as well as provide evidence to support the development of interventions and guide new studies in the region.

          Leptospirosis cases and possible environmental, socioeconomic, and livestock factors were analyzed. The study used data by municipality (all 496) obtained via an open access database. Georeferenced maps were constructed and statistical analysis performed for 26 variables. A multivariable regression analysis was carried out.

          An annual average of 428 human cases of leptospirosis was reported in the state from 2008 to 2012. The cumulative incidence in rural populations was eight times higher than in urban populations. Variables significantly associated with leptospirosis cases in the final model were: ecoregion, type of soil and to a lesser extent tobacco and rice production.

          Results showed that leptospirosis cases were concentrated in the state capital and in specific ecoregions. Environmental and agricultural production processes were identified as possible risk factors and these conditions are probably permanent characteristics of the state. This study contributes to the knowledge on leptospirosis distribution and risk factors in the state, and also highlights the importance of a holistic view and intersectoral approach in preventing the disease.

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          Most cited references25

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          Urban epidemic of severe leptospirosis in Brazil. Salvador Leptospirosis Study Group.

          Leptospirosis has, traditionally, been considered a sporadic rural disease. We describe a large urban outbreak of leptospirosis. Active surveillance for leptospirosis was established in an infectious-disease referral hospital in Salvador, Brazil, between March 10 and Nov 2, 1996. Patients meeting case criteria for severe manifestations of leptospirosis were recruited into the study. The diagnosis was confirmed in the laboratory with the microagglutination test and identification of leptospires in blood or urine. Risk factors for death were examined by multivariate analyses. Surveillance identified 326 cases of which 193 (59%) were laboratory-confirmed (133) or probable (60) cases. Leptospira interrogans serovar copenhageni was isolated from 87% of the cases with positive blood cultures. Most of the cases were adult (mean age 35.9 years [SD 15.9]), and 80% were male. Complications included jaundice (91%), oliguria (35%), and severe anaemia (26%). 50 cases died (case-fatality rate 15%) despite aggressive supportive care including dialysis (in 23%). Altered mental status was the strongest independent predictor of death (odds ratio 9.12 [95% CI 4.28-20.3]), age over 37 years, renal insufficiency, and respiratory insufficiency were also significant predictors of death. Before admission to hospital, 42% were misdiagnosed as having dengue fever in the outpatient clinic; an outbreak of dengue fever was taking place concurrently. An epidemic of leptospirosis has become a major urban health problem, associated with high mortality. Diagnostic confusion with dengue fever, another emerging infectious disease with a similar geographic distribution, prevents timely intervention that could minimise mortality.
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            Zero-inflated and hurdle models of count data with extra zeros: examples from an HIV-risk reduction intervention trial.

            In clinical trials of behavioral health interventions, outcome variables often take the form of counts, such as days using substances or episodes of unprotected sex. Classically, count data follow a Poisson distribution; however, in practice such data often display greater heterogeneity in the form of excess zeros (zero-inflation) or greater spread in the values (overdispersion) or both. Greater sample heterogeneity may be especially common in community-based effectiveness trials, where broad eligibility criteria are implemented to achieve a generalizable sample. This article reviews the characteristics of Poisson model and the related models that have been developed to handle overdispersion (negative binomial (NB) model) or zero-inflation (zero-inflated Poisson (ZIP) and Poisson hurdle (PH) models) or both (zero-inflated negative binomial (ZINB) and negative binomial hurdle (NBH) models). All six models were used to model the effect of an HIV-risk reduction intervention on the count of unprotected sexual occasions (USOs), using data from a previously completed clinical trial among female patients (N = 515) participating in community-based substance abuse treatment (Tross et al. Effectiveness of HIV/AIDS sexual risk reduction groups for women in substance abuse treatment programs: Results of NIDA Clinical Trials Network Trial. J Acquir Immune Defic Syndr 2008; 48(5):581-589). Goodness of fit and the estimates of treatment effect derived from each model were compared. The ZINB model provided the best fit, yielding a medium-sized effect of intervention. This article illustrates the consequences of applying models with different distribution assumptions on the data. If a model used does not closely fit the shape of the data distribution, the estimate of the effect of the intervention may be biased, either over- or underestimating the intervention effect.
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              Outbreak of Leptospirosis after Flood, the Philippines, 2009

              After a typhoon in September 2009, an outbreak of leptospirosis occurred in Metro Manila, the Philippines; 471 patients were hospitalized and 51 (10.8%) died. A hospital-based investigation found risk factors associated with fatal infection to be older age, hemoptysis, anuria, jaundice, and delayed treatment with antimicrobial drugs.
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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
                12 November 2015
                November 2015
                : 9
                : 11
                : e0004095
                Affiliations
                [1 ]Department of Communicable Diseases and Health Analysis, Pan American Health Organization, Washington, D.C., United States of America
                [2 ]Laboratório de Referência Nacional para Leptospirose, Centro Colaborador da Organização Mundial da Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
                [3 ]Faculdade de Medicina Veterinária, Departamento de Medicina Veterinária Preventiva, Laboratório de Epidemiologia Veterinária, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
                [4 ]Secretaria de Saúde do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
                [5 ]Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF), Fundacão Estadual de Pesquisa Agropecuária (FEPAGRO), Eldorado do Sul, Rio Grande do Sul, Brazil
                [6 ]Secretaria da Agricultura Pecuária do Sul, Porto Alegre, Rio Grande do Sul, Brazil
                [7 ]Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America
                [8 ]Laboratório de Avaliação e Promoção da Saúde Ambiental, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
                University of California, San Diego School of Medicine, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MCS PN MMP. Performed the experiments: PN MCS GM ML. Analyzed the data: MCS PN GM LGC CMZ. Contributed reagents/materials/analysis tools: PN GM. Wrote the paper: MCS PN MMP GM CBdA ROR GMC CMZ LGC ML DFB SA MAE.

                Article
                PNTD-D-15-01070
                10.1371/journal.pntd.0004095
                4643048
                26562157
                64589b63-36b5-40fc-8186-6b29cce8ee76
                Copyright @ 2015

                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
                : 18 June 2015
                : 30 August 2015
                Page count
                Figures: 6, Tables: 2, Pages: 20
                Funding
                GM received a scholarship from CNPq, Brazil. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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