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      Mortality among blood donors seropositive and seronegative for Chagas disease (1996–2000) in São Paulo, Brazil: A death certificate linkage study

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          Abstract

          Background

          Individuals in the indeterminate phase of Chagas disease are considered to have mortality rates similar to those of the overall population. This study compares mortality rates among blood donors seropositive for Chagas disease and negative controls in the city of São Paulo, Brazil.

          Methodology/principal findings

          This is a retrospective cohort study of blood donors from 1996 to 2000: 2842 seropositive and 5684 seronegative for Chagas disease. Death status was ascertained by performing probabilistic record linkage (RL) with the Brazil national mortality information system (SIM). RL was assessed in a previous validation study. Cox Regression was used to derive hazard ratios (HR), adjusting for confounders. RL identified 159 deaths among the 2842 seropositive blood donors (5.6%) and 103 deaths among the 5684 seronegative (1.8%). Out of the 159 deaths among seropositive donors, 26 had the 10th International Statistical Classification of Diseases and Related Health Problems (ICD-10) indicating Chagas disease as the underlying cause of death (B57.0/B57.5), 23 had ICD-10 codes (I42.0/I42.2/I47.0/I47.2/I49.0/I50.0/I50.1/ I50.9/I51.7) indicating cardiac abnormalities possibly related to Chagas disease listed as an underlying or associated cause of death, with the others having no mention of Chagas disease in part I of the death certificate. Donors seropositive for Chagas disease had a 2.3 times higher risk of death due to all causes (95% Confidence Interval (95% CI), 1.8–3.0) than seronegative donors. When considering deaths due to Chagas disease or those that had underlying causes of cardiac abnormalities related to Chagas disease, seropositive donors had a risk of death 17.9 (95% CI, 6.3–50.8) times greater than seronegative donors.

          Conclusions/significance

          There is an excess risk of death in donors seropositive blood for Chagas disease compared to seronegative donors. Chagas disease is an under-reported cause of death in the Brazilian mortality database.

          Author summary

          Chagas disease is classified as one of the 17 most important neglected diseases by the World Health Organization (WHO). The majority of infected individuals live in 21 countries of Central and South America. Estimates of mortality attributable to Chagas disease vary considerably (between 0.2% and 19.2% annually). To improve the measurement of disease burden and policy decision-making in regard to treatment availability, more accurate estimates of mortality, especially among otherwise asymptomatic seropositive individuals are needed,. This study compares mortality rates and causes of death of asymptomatic blood donors who tested seropositive for Chagas disease and seronegative for all screening tests conducted in Brazil. Mortality status was ascertained by linking donor names with the Brazilian national mortality information system (SIM). The study found that donors who tested Chagas disease seropositive had risk of death from all causes 2.3 (95% CI, 1.8–3.0) times greater than seronegative ones. The data also suggest that the SIM may underestimate the total number of deaths attributable to Chagas disease in Brazil.

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          Most cited references44

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          Chagas disease

          The Lancet, 375(9723), 1388-1402
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            Ten-year incidence of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi-seropositive former blood donors.

            Very few studies have measured disease penetrance and prognostic factors of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi-infected persons. We performed a retrospective cohort study among initially healthy blood donors with an index T cruzi-seropositive donation and age-, sex-, and period-matched seronegatives in 1996 to 2002 in the Brazilian cities of São Paulo and Montes Claros. In 2008 to 2010, all subjects underwent medical history, physical examination, ECGs, and echocardiograms. ECG and echocardiogram results were classified by blinded core laboratories, and records with abnormal results were reviewed by a blinded panel of 3 cardiologists who adjudicated the outcome of Chagas cardiomyopathy. Associations with Chagas cardiomyopathy were tested with multivariate logistic regression. Mean follow-up time between index donation and outcome assessment was 10.5 years for the seropositives and 11.1 years for the seronegatives. Among 499 T cruzi seropositives, 120 (24%) had definite Chagas cardiomyopathy, and among 488 T cruzi seronegatives, 24 (5%) had cardiomyopathy, for an incidence difference of 1.85 per 100 person-years attributable to T cruzi infection. Of the 120 seropositives classified as having Chagas cardiomyopathy, only 31 (26%) presented with ejection fraction <50%, and only 11 (9%) were classified as New York Heart Association class II or higher. Chagas cardiomyopathy was associated (P<0.01) with male sex, a history of abnormal ECG, and the presence of an S3 heart sound. There is a substantial annual incidence of Chagas cardiomyopathy among initially asymptomatic T cruzi-seropositive blood donors, although disease was mild at diagnosis.
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              Epidemiology, control and surveillance of Chagas disease: 100 years after its discovery.

              Chagas disease originated millions of years ago as an enzootic infection of wild animals and began to be transmitted to humans as an anthropozoonosis when man invaded wild ecotopes. While evidence of human infection has been found in mummies up to 9,000 years old, endemic Chagas disease became established as a zoonosis only in the last 200-300 years, as triatomines adapted to domestic environments. It is estimated that 15-16 million people are infected with Trypanosoma cruzi in Latin America, and 75-90 million are exposed to infection. Control of Chagas disease must be undertaken by interrupting its transmission by vectors and blood transfusions, improving housing and areas surrounding dwellings, providing sanitation education for exposed populations and treating acute and recently infected chronic cases. These measures should be complemented by surveillance and primary, secondary and tertiary care.
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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 2017
                May 2017
                : 11
                : 5
                : e0005542
                Affiliations
                [1 ]Department of Infectious Diseases, School of Medicine—University of Sao Paulo—FMUSP, Sao Paulo, Sao Paulo, Brazil
                [2 ]Institute of Education and Research, Hospital Sirio Libanes, Sao Paulo, Sao Paulo, Brazil
                [3 ]Department of Statistics, Institute of Mathematics and Statistics, University of Sao Paulo—IME-USP, Sao Paulo, Sao Paulo, Brazil
                [4 ]Fundação Pró-Sangue—Hemocenter of Sao Paulo, Sao Paulo, Sao Paulo, Brazil
                [5 ]Department of Computer Science, Institute of Mathematics and Statistics, University of Sao Paulo—IME-USP, Sao Paulo, Sao Paulo, Brazil
                [6 ]Epidemiology and Health Policy Research, Blood Systems Research Institute—BSRI, San Francisco, California, United States of America
                [7 ]Hospital das Clínicas and School of Medicine, Universidade Federal de Minas Gerais—UFMG, Belo Horizonte, Minas Gerais, Brazil
                [8 ]Department of Infectious Diseases, School of Medicine and Tropical Medicine Institute—University of Sao Paulo—FMUSP, Sao Paulo, Sao Paulo, Brazil
                Imperial College London, UNITED KINGDOM
                Author notes

                The authors have declared that no competing interests exist.

                • Conceptualization: LC ALB ECS.

                • Data curation: LC ALB.

                • Formal analysis: LC ALB APA AM ALPR JEF ECS.

                • Funding acquisition: LC ECS.

                • Methodology: LC ALB ECS.

                • Project administration: LC.

                • Writing – original draft: LC ALB ECS.

                • Writing – review & editing: LC ALB BC ALPR ECS.

                Author information
                http://orcid.org/0000-0002-3467-6805
                Article
                PNTD-D-16-01305
                10.1371/journal.pntd.0005542
                5436632
                28545053
                8f6bbefe-f667-4d33-86e5-db4723536442
                © 2017 Capuani 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
                : 21 July 2016
                : 31 March 2017
                Page count
                Figures: 2, Tables: 4, Pages: 14
                Funding
                Funded by: National Institute of Allergy and Infectious Diseases (US)
                Award ID: 1P50AI098461-01 REVISED
                Award Recipient :
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
                Award ID: 158565/2012-6
                Award Recipient :
                This work is supported and funded by the National Institute of Allergy and Infectious Disease – Grant Number 1P50AI098461-01 REVISED and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for scholarship of the Post Graduate Program - process nº 158565/2012-6. 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
                Tropical Diseases
                Neglected Tropical Diseases
                Chagas Disease
                Medicine and Health Sciences
                Parasitic Diseases
                Protozoan Infections
                Chagas Disease
                People and Places
                Demography
                Death Rates
                Medicine and Health Sciences
                Health Care
                Blood Donors
                People and places
                Geographical locations
                South America
                Brazil
                Biology and Life Sciences
                Organisms
                Protozoans
                Parasitic Protozoans
                Trypanosoma
                Trypanosoma Cruzi
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Biology and Life Sciences
                Physiology
                Body Fluids
                Blood
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Blood
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Serology
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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