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      Global Morbidity and Mortality of Leptospirosis: A Systematic Review

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          Abstract

          Background

          Leptospirosis, a spirochaetal zoonosis, occurs in diverse epidemiological settings and affects vulnerable populations, such as rural subsistence farmers and urban slum dwellers. Although leptospirosis is a life-threatening disease and recognized as an important cause of pulmonary haemorrhage syndrome, the lack of global estimates for morbidity and mortality has contributed to its neglected disease status.

          Methodology/Principal Findings

          We conducted a systematic review of published morbidity and mortality studies and databases to extract information on disease incidence and case fatality ratios. Linear regression and Monte Carlo modelling were used to obtain age and gender-adjusted estimates of disease morbidity for countries and Global Burden of Disease (GBD) and WHO regions. We estimated mortality using models that incorporated age and gender-adjusted disease morbidity and case fatality ratios. The review identified 80 studies on disease incidence from 34 countries that met quality criteria. In certain regions, such as Africa, few quality assured studies were identified. The regression model, which incorporated country-specific variables of population structure, life expectancy at birth, distance from the equator, tropical island, and urbanization, accounted for a significant proportion (R 2 = 0.60) of the variation in observed disease incidence. We estimate that there were annually 1.03 million cases (95% CI 434,000–1,750,000) and 58,900 deaths (95% CI 23,800–95,900) due to leptospirosis worldwide. A large proportion of cases (48%, 95% CI 40–61%) and deaths (42%, 95% CI 34–53%) were estimated to occur in adult males with age of 20–49 years. Highest estimates of disease morbidity and mortality were observed in GBD regions of South and Southeast Asia, Oceania, Caribbean, Andean, Central, and Tropical Latin America, and East Sub-Saharan Africa.

          Conclusions/Significance

          Leptospirosis is among the leading zoonotic causes of morbidity worldwide and accounts for numbers of deaths, which approach or exceed those for other causes of haemorrhagic fever. Highest morbidity and mortality were estimated to occur in resource-poor countries, which include regions where the burden of leptospirosis has been underappreciated.

          Author Summary

          Leptospirosis is a zoonotic bacterial disease that affects vulnerable populations such as rural subsistence farmers and urban slum dwellers. Although leptospirosis causes life-threatening clinical manifestations, such as pulmonary hemorrhage syndrome, and has a worldwide distribution, the key barrier to addressing this neglected disease has been insufficient data on its disease burden. We searched published literature and grey literature studies on leptospirosis and using information collected on disease incidence and case fatality, estimated leptospirosis incidence and mortality at country, regional and global level. Overall leptospirosis was estimated to cause 1.03 million cases and 58,900 deaths each year. These estimates place leptospirosis as a leading zoonotic cause of morbidity and mortality. In addition, morbidity and mortality was greatest in the poorest regions of the world and in areas where surveillance is not routinely performed.

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          Most cited references60

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          Impact of regional climate change on human health.

          The World Health Organisation estimates that the warming and precipitation trends due to anthropogenic climate change of the past 30 years already claim over 150,000 lives annually. Many prevalent human diseases are linked to climate fluctuations, from cardiovascular mortality and respiratory illnesses due to heatwaves, to altered transmission of infectious diseases and malnutrition from crop failures. Uncertainty remains in attributing the expansion or resurgence of diseases to climate change, owing to lack of long-term, high-quality data sets as well as the large influence of socio-economic factors and changes in immunity and drug resistance. Here we review the growing evidence that climate-health relationships pose increasing health risks under future projections of climate change and that the warming trend over recent decades has already contributed to increased morbidity and mortality in many regions of the world. Potentially vulnerable regions include the temperate latitudes, which are projected to warm disproportionately, the regions around the Pacific and Indian oceans that are currently subjected to large rainfall variability due to the El Niño/Southern Oscillation sub-Saharan Africa and sprawling cities where the urban heat island effect could intensify extreme climatic events.
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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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              Leptospirosis: a zoonotic disease of global importance

              In the past decade, leptospirosis has emerged as a globally important infectious disease. It occurs in urban environments of industrialised and developing countries, as well as in rural regions worldwide. Mortality remains significant, related both to delays in diagnosis due to lack of infrastructure and adequate clinical suspicion, and to other poorly understood reasons that may include inherent pathogenicity of some leptospiral strains or genetically determined host immunopathological responses. Pulmonary haemorrhage is recognised increasingly as a major, often lethal, manifestation of leptospirosis, the pathogenesis of which remains unclear. The completion of the genome sequence of Leptospira interrogans serovar lai, and other continuing leptospiral genome sequencing projects, promise to guide future work on the disease. Mainstays of treatment are still tetracyclines and beta-lactam/cephalosporins. No vaccine is available. Prevention is largely dependent on sanitation measures that may be difficult to implement, especially in developing countries.
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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
                17 September 2015
                September 2015
                : 9
                : 9
                : e0003898
                Affiliations
                [1 ]Oswaldo Cruz Foundation, Brazilian Ministry of Health, Salvador, Bahia, Brazil
                [2 ]Institute of Collective Health, Federal University of Bahia, UFBA, Salvador, Brazil
                [3 ]Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America
                [4 ]Center for Analytical Sciences, Yale School of Public Health, New Haven, Connecticut, United States of America
                [5 ]Section of Epidemiology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland
                [6 ]Division of Information, Evidence, Research and Innovation, World Health Organization, Regional Office for Europe, UN City, Copenhagen Ø, Denmark
                [7 ]Department for the Control of Neglected Tropical Diseases, World Health Organization, Genève, Switzerland
                University of Tennessee, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CS BAR AIK. Performed the experiments: FC JEH JC MK PT MSMS. Analyzed the data: FC JEH JC MK PT AIK. Contributed reagents/materials/analysis tools: AIK CS BAR. Wrote the paper: FC JEH AIK BAR.

                Article
                PNTD-D-15-00394
                10.1371/journal.pntd.0003898
                4574773
                26379143
                b54fb2a7-9c0c-4ec3-a068-895a1ca7170a
                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
                : 11 March 2015
                : 10 June 2015
                Page count
                Figures: 4, Tables: 3, Pages: 19
                Funding
                This work was supported by the World Health Organization, Brazilian Ministry of Education, National Institutes of Health (R01 AI052473, U01 AI088752, D43 TW00919, R25 TW009338, T32 AI007172, R24 TW007988) and Wellcome Trust (102330/Z/13/Z). 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
                Data are available at the following website: http://www.who.int/zoonoses/diseases/lerg/en/

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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