<?xml version="1.0" encoding="UTF-8" standalone="no"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" "journalpublishing.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="research-article" dtd-version="2.3" xml:lang="EN">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Parasitol.</journal-id>
<journal-title>Frontiers in Parasitology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Parasitol.</abbrev-journal-title>
<issn pub-type="epub">2813-2424</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fpara.2023.1195646</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Parasitology</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Diagnosis and management of chagasic cardiomyopathy patients in several institutions in Argentina</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Chuit</surname>
<given-names>Roberto</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1750027"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Antonietti</surname>
<given-names>Laura</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2262335"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ag&#xfc;ero</surname>
<given-names>Roberto Nicol&#xe1;s</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1865756"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Varela</surname>
<given-names>Gabriela Badino</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mordini</surname>
<given-names>Oscar Daniel</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Alemandri</surname>
<given-names>Emilce</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Abril</surname>
<given-names>Marcelo</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1219691"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>D&#xed;as</surname>
<given-names>Miguel</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yad&#xf3;n</surname>
<given-names>Zaida E.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pizzi</surname>
<given-names>Hugo</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pizzi</surname>
<given-names>Rogelio</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2272405"/>
</contrib>
</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Instituto de Investigaciones Epidemiol&#xf3;gicas, Academia Nacional de Medicina</institution>, <addr-line>Buenos Aires</addr-line>, <country>Argentina</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Fundaci&#xf3;n Mundo Sano</institution>, <addr-line>Buenos Aires</addr-line>, <country>Argentina</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>Hospital Rawson, Ministerio de Salud</institution>, <addr-line>Cordoba</addr-line>, <country>Argentina</country>
</aff>
<aff id="aff4">
<sup>4</sup>
<institution>Facultad de Ciencias Medicas de Cordoba, Universidad Nacional de Cordoba</institution>, <addr-line>Cordoba</addr-line>, <country>Argentina</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: David Carmena, Carlos III Health Institute (ISCIII), Spain</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Pau Bosch-Nicolau, Vall d&#x2019;Hebron University Hospital, Spain; Joao Santana Silva, Oswaldo Cruz Foundation (Fiocruz), Brazil</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Roberto Chuit, <email xlink:href="mailto:chuit@aya.yale.edu">chuit@aya.yale.edu</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>24</day>
<month>07</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="collection">
<year>2023</year>
</pub-date>
<volume>2</volume>
<elocation-id>1195646</elocation-id>
<history>
<date date-type="received">
<day>28</day>
<month>03</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>23</day>
<month>06</month>
<year>2023</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2023 Chuit, Antonietti, Ag&#xfc;ero, Varela, Mordini, Alemandri, Abril, D&#xed;as, Yad&#xf3;n, Pizzi and Pizzi</copyright-statement>
<copyright-year>2023</copyright-year>
<copyright-holder>Chuit, Antonietti, Ag&#xfc;ero, Varela, Mordini, Alemandri, Abril, D&#xed;as, Yad&#xf3;n, Pizzi and Pizzi</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec>
<title>Introduction</title>
<p>According to estimates by the World Health Organization, the infection and disease caused by the protozoan parasite <italic>Trypanosoma cruzi</italic> affects almost 6 million people, and more than 1 million suffer chagasic cardiomyopathy (Ch-CMP). It is estimated that 376,000 of these individuals live in Argentina. This study describes the characteristics and medical management of individuals with Ch-CMP in Argentina.</p>
</sec>
<sec>
<title>Methods</title>
<p>This is a descriptive, retrospective, cross-sectional study on the diagnosis and clinical and therapeutic evaluation of patients with Ch-MCP using historical records collected from different medical institutions in the country between 1 January 2018 and 30 June 2021.</p>
</sec>
<sec>
<title>Results</title>
<p>During this period, 652 patients (mean age 61.2 years&#xa0;&#xb1;&#xa0;12.9) were included, with women accounting for 60.3% of the sample. The diagnosis of cardiac insufficiency was 36.0% and 64.4% had arrhythmias. The most common cardiovascular risk factors detected were arterial hypertension (69.5%), smoking (56.6%), and diabetes (20.9%). Less than half of the subjects (45.4%) had been studied by electrocardiogram (ECG), chest X-ray, and echocardiogram. ECG studies showed conduction disorders (38.8%), left ventricular hypertrophy (28.1%), ventricular extrasystoles (22.0%), complete right bundle branch block (8.6%), and atrioventricular block (2.6%). According to the Kuschnir classification, 21.4% of the study subjects were in Grade 3.</p>
</sec>
<sec>
<title>Conclusions</title>
<p>The patients included in the study had a similar clinical presentation and history of the disease to those published in other studies. When evaluating the medical practices, we found that patients were inadequately studied. Although it is difficult to estimate the fraction of the total number of patients represented by the present study, the study allowed us to establish that the care received by patients was not adequate.</p>
</sec>
</abstract>
<kwd-group>
<kwd>Chagas disease</kwd>
<kwd>cardiomyopathy</kwd>
<kwd>diagnosis and management</kwd>
<kwd>heart failure</kwd>
<kwd>Argentina</kwd>
</kwd-group>
<counts>
<fig-count count="1"/>
<table-count count="3"/>
<equation-count count="0"/>
<ref-count count="39"/>
<page-count count="7"/>
<word-count count="3276"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Parasite Diagnostics</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro">
<label>1</label>
<title>Introduction</title>
<p>Chagas disease (ChD), or American trypanosomiasis, is a parasitic disease originally from the Americas, caused by <italic>Trypanosoma cruzi</italic> and described by Carlos Chagas at the beginning of the 20th century (<xref ref-type="bibr" rid="B6">Coura and Borges-Pereira, 2010</xref>). The first reports of cardiac manifestations and/or alterations were recorded by Salvador Mazza in 1926 (<xref ref-type="bibr" rid="B22">Mazza and Jorg, 1936</xref>), which included hypotension and splitting of the second heart sound, and were reinforced in the mid-1950s (<xref ref-type="bibr" rid="B33">Rosenbaum, 1964</xref>; <xref ref-type="bibr" rid="B28">Pinto Dias, 1982</xref>).</p>
<p>The World Health Organization (WHO) estimates that <italic>T. cruzi</italic> infection and illness affects almost 6 million people (Chagas disease in Latin America: an epidemiological update based on 2010 estimates). Over 1 million of these individuals suffer chagasic cardiomyopathy (Ch-CMP), and 376,000 live in Argentina.</p>
<p>ChD is endemic in areas of Latin America that were initially associated with vector transmission. Nonetheless, in recent decades, the disease&#x2019;s detection has increased in non-endemic regions. It requires medical attention, mainly because of population migratory processes (<xref ref-type="bibr" rid="B34">Schmunis and Yadon, 2010</xref>).</p>
<p>When infection occurs, the acute stage of the disease is usually asymptomatic or oligosymptomatic. In most cases, the chronic phase evolves into an indeterminate form, characterized by positive serology without evidence of organic involvement; people who develop clinical manifestations are usually affected by myocardial disease, digestive disease, or both (<xref ref-type="bibr" rid="B31">Ribeiro et&#xa0;al., 2012</xref>). Chagasic cardiomyopathy (Ch-CMP) is characterized by progression toward myocardial compromise, which may present with normal ECG findings, minimal electrocardiographic (<xref ref-type="bibr" rid="B29">Pinto Dias, 1985</xref>) alterations, or even dilated cardiac chambers with a general deterioration of ventricular function, manifesting as cardiac insufficiency (<xref ref-type="bibr" rid="B20">Marin Neto et&#xa0;al., 2013</xref>; <xref ref-type="bibr" rid="B19">Mar&#xed;n-Neto et&#xa0;al., 2015</xref>; <xref ref-type="bibr" rid="B25">Nunes et&#xa0;al., 2018</xref>).</p>
<p>The disease&#x2019;s leading clinical and organic manifestation is cardiac and is associated with premature cardiovascular morbi-mortality, mainly by sudden death, followed by cardiac insufficiency and thromboembolism (<xref ref-type="bibr" rid="B4">Biolo et&#xa0;al., 2010</xref>; <xref ref-type="bibr" rid="B30">Rassi et&#xa0;al., 2010</xref>). Although there are regional variations (<xref ref-type="bibr" rid="B21">Martins-Melo and Heukelbach, 2013</xref>), in Argentina, it is estimated that 1% of patients with Ch-CMP will die from cardiac insufficiency (<xref ref-type="bibr" rid="B18">Manzullo and Chuit, 1999</xref>; <xref ref-type="bibr" rid="B39">Viotti et&#xa0;al., 2006</xref>). The factors associated with an increased risk of the development of myocardiopathy are still not completely understood (<xref ref-type="bibr" rid="B12">Elizari, 1999</xref>). There is debate surrounding if the parasite has direct involvement in causing a direct lesion (<xref ref-type="bibr" rid="B3">Bellotti et&#xa0;al., 1996</xref>), an autoimmune phenomenon (<xref ref-type="bibr" rid="B38">Takle and Hudson, 1989</xref>), or mixed mechanisms with microvascular alterations and autonomic denervation (<xref ref-type="bibr" rid="B9">D&#xe1;vila-Spinetti et&#xa0;al., 2005</xref>). Therefore, it is possible to estimate that the organic manifestation of the disease is the result of multifactorial processes (<xref ref-type="bibr" rid="B23">Medina-Rinc&#xf3;n et&#xa0;al., 2021</xref>).</p>
<p>Moreover, although the prevention and control of ChD, as well as a general improvement in quality of life, has contributed to a decrease in the incidence of the disease, there is still a deficit in access to and the quality of medical care for chagasic patients. Approximately 10% of the individuals infected with <italic>T. cruzi</italic> have access to early diagnosis, and only 1% have access to timely and adequate treatment (<xref ref-type="bibr" rid="B23">Medina-Rinc&#xf3;n et&#xa0;al., 2021</xref>). Among the causes of this phenomenon are a lack of specific knowledge from the health personnel; the silent nature of the disease, which affects mainly rural populations; and barriers to health services for the patients (<xref ref-type="bibr" rid="B14">Fanjul et&#xa0;al., 2016</xref>).</p>
<p>This study aims to describe the characteristics of a cohort of patients with Ch-CMP and the medical attention they received in institutions providing low and medium levels of medical care across diverse regions of Argentina. The objective is to provide knowledge and evidence that can be used in decision-making processes to support prompt diagnosis, follow-up, and treatment.</p>
</sec>
<sec id="s2">
<label>2</label>
<title>Methods</title>
<p>A cross-sectional, descriptive, and retrospective study of hospital-based medical practices (diagnosis, clinical evaluation, and treatment) was performed for individuals diagnosed with Ch-CMP, whose information was collected through a network of professionals coordinated by the Institute of Epidemiological Research, National Academy of Medicine of Buenos Aires. The data were collected through a specifically designed structured questionnaire that was accessible through the internet (web based).</p>
<p>The data collected were obtained from the medical records of patients who received on-site or off-site diagnostic tests and complementary studies from low- and medium-capability institutions, such as an electrocardiogram, radiology, ultrasound, a stress exercise test, and a Holter monitor. The historical data collected were obtained from records of patients that received medical attention between January 2018 and June 2021, provided by professionals from various states of Argentina (Chaco, C&#xf3;rdoba, Corrientes, Formosa, Salta, Jujuy, Tucum&#xe1;n, Ciudad de Buenos Aires, and Buenos Aires) associated with the coordinating institution. As the study focused on the medical care received, the facilities and areas of Argentina where they were located were undifferentiated.</p>
<p>The inclusion criteria in the current study were patients &#x2265;&#xa0;18 years of age with a recorded diagnosis of ChD infection as outlined by national (<xref ref-type="bibr" rid="B13">Enfermedades Infecciosas, 2018</xref>) and international guidelines (<xref ref-type="bibr" rid="B7">Cucunub&#xe1; et&#xa0;al., 2017</xref>; <xref ref-type="bibr" rid="B26">Pan American Health Organization (2019)</xref> (two positive serologic tests) and with a myocardiopathy diagnosis.</p>
<p>Ch-CMP was defined by the existence of one or more of the following alterations: a) ECG disorder: complete blockage of right bundle branch (RBBB); Left anterior fascicular block (LAFB); RBBB + LAFB; first degree atrioventricular (AV) block or greater; atrial flutter (AF) /atrial fibrillation (AF); ventricular extrasystoles (VE); or b) ECG disorders: systolic diameter of the left ventricle &gt; 55 mm; ejection fraction (EFy) &lt; 50%; ventricular aneurysm or apical or posterior-basal segmental wall motion informed as moderate to severe in the history report file.</p>
<p>Tobacco consumption, alcohol consumption, hypertension, diabetes, dyslipidemia, and other pathologies obtained from clinical records from the medical institution&#x2019;s history file were registered.</p>
<p>To determine the functional capacity of the heart, the records were stratified according to the Kuschnir classification (<xref ref-type="bibr" rid="B17">Kuschnir et&#xa0;al., 1985</xref>), which establishes four stages (0 to 3) based on the evaluation of complementary basic tests and diagnosis of cardiac insufficiency.</p>
</sec>
<sec id="s3" sec-type="results">
<label>3</label>
<title>Results</title>
<p>Of 1,150 records analyzed, 652 patients fulfilled the inclusion criteria, presenting positive serologic tests for <italic>T. cruzi</italic> and Ch-CMP. The mean age of cases was 61.2 years (SD&#xa0;&#xb1;&#xa0;12.9). In addition, 393 (60.3%) were female and 259 (39.7%) male.</p>
<p>The most prevalent cardiovascular risk factors were hypertension (<italic>n</italic>&#xa0;=&#xa0;453; 69.5%), smoking (<italic>n</italic>&#xa0;=&#xa0;369; 56.6%), dyslipidemias (<italic>n</italic>= 248: 38,1%), and diabetes (<italic>n</italic>&#xa0;=&#xa0;136; 20,9%). (<xref ref-type="table" rid="T1">
<bold>Table&#xa0;1</bold>
</xref>).</p>
<table-wrap id="T1" position="float">
<label>Table&#xa0;1</label>
<caption>
<p>Prior pathological history of patients with chagasic cardiomyopathy (Ch-CMP).</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">Condition</th>
<th valign="top" align="center">n</th>
<th valign="top" align="center">%</th>
</tr>
</thead>
<tbody>
<tr>
<th valign="top" colspan="3" align="left">Factors for cardiovascular risk</th>
</tr>
<tr>
<td valign="top" align="left">Arterial hypertension</td>
<td valign="top" align="center">453</td>
<td valign="top" align="center">69.5</td>
</tr>
<tr>
<td valign="top" align="left">Smoking</td>
<td valign="top" align="center">369</td>
<td valign="top" align="center">56.6</td>
</tr>
<tr>
<td valign="top" align="left">Dyslipidemia</td>
<td valign="top" align="center">248</td>
<td valign="top" align="center">38.1</td>
</tr>
<tr>
<td valign="top" align="left">Diabetes</td>
<td valign="top" align="center">136</td>
<td valign="top" align="center">20.9</td>
</tr>
<tr>
<th valign="top" colspan="3" align="left">Prior pathological history</th>
</tr>
<tr>
<td valign="top" align="left">Chronic obstructive pulmonary disease (COPD)</td>
<td valign="top" align="center">74</td>
<td valign="top" align="center">11.3</td>
</tr>
<tr>
<td valign="top" align="left">Chronic renal insufficiency</td>
<td valign="top" align="center">65</td>
<td valign="top" align="center">10.0</td>
</tr>
<tr>
<td valign="top" align="left">Chronic liver disease</td>
<td valign="top" align="center">53</td>
<td valign="top" align="center">8.1</td>
</tr>
<tr>
<td valign="top" align="left">Cerebrovascular accident (CVA)/Transient ischemic attack (TIA)</td>
<td valign="top" align="center">25</td>
<td valign="top" align="center">3.8</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Cohort of 652 patients in Argentina between January 2018 and June 2021.</p>
</fn>
<fn>
<p>Source: Institute of Epidemiological Research, National Academy of Science of Buenos Aires.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>The distribution of cardiac insufficiency (CI) in patients with chagasic cardiomyopathy (Ch-CMP) by age group (n&#xa0;=&#xa0;235) is presented in <xref ref-type="fig" rid="f1">
<bold>Figure&#xa0;1</bold>
</xref>. Although this condition affected individuals ranging from 30 years of age to older than 80 years of age, incidence increased with age and was higher in those older than 55 years, who represented 79.9% of the study population and 95.7% of the cases with CI.</p>
<fig id="f1" position="float">
<label>Figure&#xa0;1</label>
<caption>
<p>Distribution of cardiac insufficiency (CI) by age group in patients with chagasic cardiomyopathy (Ch-CMP). Cohort of 652 patients in Argentina between January 2018 and June 2021. <italic>Source</italic>: Institute of Epidemiological Research, National Academy of Medicine of Buenos Aires.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fpara-02-1195646-g001.tif"/>
</fig>
<p>Of 420 patients presented with arrhythmias, 128 (30.5%) presented with ventricular arrhythmias and 85 (20.2%) presented with fibrillation or atrial flutter. The type of arrhythmia was not specified in 207 (49.3%) patients. The history of cardiac device implantations was recorded in only 32 patients older than 50 years.</p>
<p>Medical practices performed on these patients are shown in <xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref>. ECG (93.3%) was the most performed medical exam, followed by a thoracic X-ray (73.6%), stress exercise test (SET) (70.1%), echocardiogram (46.0%), and Holter monitor (38.2%). Less than half of the patients (n&#xa0;=&#xa0;296; 45.4%) have records for ECG, chest X-Ray, and echocardiogram.</p>
<table-wrap id="T2" position="float">
<label>Table&#xa0;2</label>
<caption>
<p>Distribution of diagnostic tests reported in patients with chagasic cardiomyopathy (Ch-CMP) by age.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" rowspan="2" align="left">Age range</th>
<th valign="top" rowspan="2" align="center">n</th>
<th valign="top" colspan="2" align="center">Electrocardiogram (ECG)</th>
<th valign="top" colspan="2" align="center">Stress exercise test (SET)</th>
<th valign="top" colspan="2" align="center">Holter monitor</th>
<th valign="top" colspan="2" align="center">Chest X-ray</th>
<th valign="top" colspan="2" align="center">Echocardiogram</th>
</tr>
<tr>
<th valign="top" align="center">n</th>
<th valign="top" align="center">%</th>
<th valign="top" align="center">n</th>
<th valign="top" align="center">%</th>
<th valign="top" align="center">n</th>
<th valign="top" align="center">%</th>
<th valign="top" align="center">n</th>
<th valign="top" align="center">%</th>
<th valign="top" align="center">n</th>
<th valign="top" align="center">%</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">30&#x2013;34</td>
<td valign="top" align="center">10</td>
<td valign="top" align="center">9</td>
<td valign="top" align="center">90.0</td>
<td valign="top" align="center">7</td>
<td valign="top" align="center">70.0</td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">40.0</td>
<td valign="top" align="center">6</td>
<td valign="top" align="center">60.0</td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">40.0</td>
</tr>
<tr>
<td valign="top" align="left">35&#x2013;39</td>
<td valign="top" align="center">34</td>
<td valign="top" align="center">32</td>
<td valign="top" align="center">94.1</td>
<td valign="top" align="center">27</td>
<td valign="top" align="center">79.4</td>
<td valign="top" align="center">10</td>
<td valign="top" align="center">29.4</td>
<td valign="top" align="center">22</td>
<td valign="top" align="center">64.7</td>
<td valign="top" align="center">18</td>
<td valign="top" align="center">52.9</td>
</tr>
<tr>
<td valign="top" align="left">40&#x2013;44</td>
<td valign="top" align="center">33</td>
<td valign="top" align="center">30</td>
<td valign="top" align="center">90.9</td>
<td valign="top" align="center">24</td>
<td valign="top" align="center">72.7</td>
<td valign="top" align="center">13</td>
<td valign="top" align="center">39.4</td>
<td valign="top" align="center">26</td>
<td valign="top" align="center">78.8</td>
<td valign="top" align="center">13</td>
<td valign="top" align="center">39.4</td>
</tr>
<tr>
<td valign="top" align="left">45&#x2013;49</td>
<td valign="top" align="center">34</td>
<td valign="top" align="center">32</td>
<td valign="top" align="center">94.1</td>
<td valign="top" align="center">24</td>
<td valign="top" align="center">70.6</td>
<td valign="top" align="center">9</td>
<td valign="top" align="center">26.5</td>
<td valign="top" align="center">25</td>
<td valign="top" align="center">73.5</td>
<td valign="top" align="center">19</td>
<td valign="top" align="center">55.9</td>
</tr>
<tr>
<td valign="top" align="left">50&#x2013;54</td>
<td valign="top" align="center">96</td>
<td valign="top" align="center">84</td>
<td valign="top" align="center">87.5</td>
<td valign="top" align="center">54</td>
<td valign="top" align="center">56.2</td>
<td valign="top" align="center">34</td>
<td valign="top" align="center">35.4</td>
<td valign="top" align="center">60</td>
<td valign="top" align="center">62.5</td>
<td valign="top" align="center">51</td>
<td valign="top" align="center">53.1</td>
</tr>
<tr>
<td valign="top" align="left">55&#x2013;59</td>
<td valign="top" align="center">101</td>
<td valign="top" align="center">97</td>
<td valign="top" align="center">96.0</td>
<td valign="top" align="center">74</td>
<td valign="top" align="center">73.3</td>
<td valign="top" align="center">35</td>
<td valign="top" align="center">34.7</td>
<td valign="top" align="center">66</td>
<td valign="top" align="center">65.3</td>
<td valign="top" align="center">48</td>
<td valign="top" align="center">47.5</td>
</tr>
<tr>
<td valign="top" align="left">60&#x2013;64</td>
<td valign="top" align="center">123</td>
<td valign="top" align="center">123</td>
<td valign="top" align="center">100.0</td>
<td valign="top" align="center">103</td>
<td valign="top" align="center">83.7</td>
<td valign="top" align="center">42</td>
<td valign="top" align="center">34.1</td>
<td valign="top" align="center">113</td>
<td valign="top" align="center">91.9</td>
<td valign="top" align="center">58</td>
<td valign="top" align="center">47.2</td>
</tr>
<tr>
<td valign="top" align="left">65&#x2013;69</td>
<td valign="top" align="center">46</td>
<td valign="top" align="center">38</td>
<td valign="top" align="center">82.6</td>
<td valign="top" align="center">21</td>
<td valign="top" align="center">45.7</td>
<td valign="top" align="center">13</td>
<td valign="top" align="center">28.3</td>
<td valign="top" align="center">30</td>
<td valign="top" align="center">65.2</td>
<td valign="top" align="center">17</td>
<td valign="top" align="center">37.0</td>
</tr>
<tr>
<td valign="top" align="left">70&#x2013;74</td>
<td valign="top" align="center">102</td>
<td valign="top" align="center">90</td>
<td valign="top" align="center">88.2</td>
<td valign="top" align="center">61</td>
<td valign="top" align="center">59.8</td>
<td valign="top" align="center">39</td>
<td valign="top" align="center">38.2</td>
<td valign="top" align="center">66</td>
<td valign="top" align="center">64.7</td>
<td valign="top" align="center">40</td>
<td valign="top" align="center">39.2</td>
</tr>
<tr>
<td valign="top" align="left">75&#x2013;79</td>
<td valign="top" align="center">38</td>
<td valign="top" align="center">38</td>
<td valign="top" align="center">100.0</td>
<td valign="top" align="center">33</td>
<td valign="top" align="center">86.8</td>
<td valign="top" align="center">22</td>
<td valign="top" align="center">57.9</td>
<td valign="top" align="center">36</td>
<td valign="top" align="center">94.7</td>
<td valign="top" align="center">19</td>
<td valign="top" align="center">50.0</td>
</tr>
<tr>
<td valign="top" align="left">&gt;&#xa0;80</td>
<td valign="top" align="center">35</td>
<td valign="top" align="center">35</td>
<td valign="top" align="center">100.0</td>
<td valign="top" align="center">29</td>
<td valign="top" align="center">82.9</td>
<td valign="top" align="center">28</td>
<td valign="top" align="center">80.0</td>
<td valign="top" align="center">30</td>
<td valign="top" align="center">85.7</td>
<td valign="top" align="center">13</td>
<td valign="top" align="center">37.1</td>
</tr>
<tr>
<td valign="top" align="left">
<bold>Total</bold>
</td>
<td valign="top" align="center">
<bold>652</bold>
</td>
<td valign="top" align="center">
<bold>608</bold>
</td>
<td valign="top" align="center">
<bold>93.3</bold>
</td>
<td valign="top" align="center">
<bold>457</bold>
</td>
<td valign="top" align="center">
<bold>70.1</bold>
</td>
<td valign="top" align="center">
<bold>249</bold>
</td>
<td valign="top" align="center">
<bold>38.2</bold>
</td>
<td valign="top" align="center">
<bold>480</bold>
</td>
<td valign="top" align="center">
<bold>73.6</bold>
</td>
<td valign="top" align="center">
<bold>300</bold>
</td>
<td valign="top" align="center">
<bold>46.0</bold>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Cohort of 652 patients in Argentina between January 2018 and June 2021.</p>
</fn>
<fn>
<p>Source: Institute of Epidemiological Research, National Academy of Science of Buenos Aires.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>In 608 patients, 1,254 electrocardiographic alterations were recorded: 408 (38.8%) patients presented with unspecific disorders of conduction, 352 (28.1%) with left ventricular hypertrophy, 276 (22.0%) with ventricular extrasystole, 108 (8.6%) with complete right bundle branch block, and 32 (2.6%) with atrioventricular block. The chest X-Ray performed on 480 individuals detected an increase in the cardiac silhouette in 334 individuals (69.6%). The SET was performed in 457 individuals, with most of the results showing no alterations (n&#xa0;=&#xa0;387; 84.6%) and 70 (15.4%) patients presenting with an abnormal result. The most common alterations were related to repolarization disorders (n&#xa0;=&#xa0;38; 54.3%), followed by ventricular arrhythmias (n&#xa0;=&#xa0;18; 25.7%), isolated supraventricular arrhythmias (n&#xa0;=&#xa0;7; 1.0%), and frequent ventricular extrasystole during maximum stress (n&#xa0;=&#xa0;7; 1.0%).</p>
<p>In total, 249 24-hour Holter ECGs were performed, of which 116 (46.6%) presented alterations: 90 (77.6%) with ventricular extrasystole, 23 (19.8%) with supraventricular and extrasystole, and 3 (2.6%) with ventricular tachycardia. In addition, 23 (19.8%) records were associated with &gt;&#xa0;2-second pauses.</p>
<p>Radio-isotopic tests were performed in only 16 (2.5%) registered patients: four (25.0%) had severe anterolateral ischemia, ventricular dilation, and deterioration of the ventricular function, while nine (56.3%) did not have any evidence of pathology. In four (25.0%) patients, dilation of the left ventricular cavity and severe global hypokinesia were recorded.</p>
<p>When analyzing registered treatments, specific antiparasitic treatment (without differentiation between benznidazole and nifurtimox) was given to 39 (6.0%) patients, aldosterone antagonists to 311 (47.7%) patients, angiotensin-converting enzyme inhibitors to 275 (42.2%) patients, beta-blockers to 181 (27.8%) patients, angiotensin II receptor antagonists (AIIRA) to 178 (27.3%) patients, diuretics to 116 (17,8%) patients, and only one of those registered had amiodarone as an indication</p>
<p>Concerning the reported hospital admissions from June 2020 to June 2021, 103 (15.8%) patients were admitted due to ChD. Some of these patients were admitted only once (n&#xa0;=&#xa0;23; 22.3%), some were admitted twice (n&#xa0;=&#xa0;68; 66.0%), and 12 (11,7%) had three or more admissions. The age range of individuals with the highest need for hospital admission was between 50 and 69 years old.</p>
<p>To determine the functional capacity of the heart in this cohort of patients, the records were distributed according to the Kuschnir classification. A total number of 504 patients could be classified as follows (<xref ref-type="table" rid="T3">
<bold>Table&#xa0;3</bold>
</xref>): 181 (35.9%) as Grade 1, 215 (42.7%) as Grade 2, and 108 (21.4%) as Grade 3. Of those in Grade 3, 33 (30.6%) required one or more admissions in the last year.</p>
<table-wrap id="T3" position="float">
<label>Table&#xa0;3</label>
<caption>
<p>Distribution of patients with heart disease according to the Kuschnir classification.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" rowspan="4" align="left">No. of hospital admissions</th>
<th valign="top" colspan="6" align="center">Kuschnir Classification</th>
</tr>
<tr>
<th valign="top" colspan="2" align="center">Grade 1</th>
<th valign="top" colspan="2" align="center">Grade 2</th>
<th valign="top" colspan="2" align="center">Grade 3</th>
</tr>
<tr>
<th valign="top" colspan="2" align="center">(n&#xa0;=&#xa0;181)</th>
<th valign="top" colspan="2" align="center">(n&#xa0;=&#xa0;215)</th>
<th valign="top" colspan="2" align="center">(n&#xa0;=&#xa0;108)</th>
</tr>
<tr>
<th valign="top" align="center">n</th>
<th valign="top" align="center">%</th>
<th valign="top" align="center">n</th>
<th valign="top" align="center">%</th>
<th valign="top" align="center">n</th>
<th valign="top" align="center">%</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">1</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">0.55</td>
<td valign="top" align="center">12</td>
<td valign="top" align="center">5.6</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">2.8</td>
</tr>
<tr>
<td valign="top" align="left">2</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center">42</td>
<td valign="top" align="center">19.5</td>
<td valign="top" align="center">26</td>
<td valign="top" align="center">24.1</td>
</tr>
<tr>
<td valign="top" align="left">3</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center">8</td>
<td valign="top" align="center">3.7</td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">3.7</td>
</tr>
<tr>
<td valign="top" align="left">Total</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">0.55</td>
<td valign="top" align="center">62</td>
<td valign="top" align="center">28.8</td>
<td valign="top" align="center">33</td>
<td valign="top" align="center">30.6</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Cohort of 504 patients in Argentina between June 2020 and June 2021.</p>
</fn>
<fn>
<p>Source: Institute of Epidemiological Research, National Academy of Science of Buenos Aires.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s4" sec-type="discussion">
<label>4</label>
<title>Discussion</title>
<p>The current study describes the clinical and epidemiological characteristics of and the medical attention received by a cohort of patients with Ch-CMP from historical clinical records from Argentina.</p>
<p>Data from these records show that women (60.3%) seek medical attention more often than men, which may be explained by cultural, labor, or social factors (<xref ref-type="bibr" rid="B17">Kuschnir et&#xa0;al., 1985</xref>; <xref ref-type="bibr" rid="B32">Rosa-Jim&#xe9;nez et&#xa0;al., 2005</xref>). This should be studied in greater depth, although a recent study showed between-sex differences, with men having a higher incidence of myocardial fibrosis and worse ventricular remodeling than women (<xref ref-type="bibr" rid="B1">Assun&#xe7;&#xe3;o et&#xa0;al., 2016</xref>).</p>
<p>The average age of patients was in line with other hospital-based studies, where advancing age is one of the established risk factors for progression to Ch-MCP, as shown by our research and analyzed by other authors (<xref ref-type="bibr" rid="B11">Echalar et&#xa0;al., 2021</xref>).</p>
<p>In the analysis of risk factors and comorbidities, our study shows similar results to those registered in other studies of individuals with PMC. (<xref ref-type="bibr" rid="B15">Freitas Lidani et&#xa0;al., 2020</xref>; <xref ref-type="bibr" rid="B8">Cutshaw et&#xa0;al., 2023</xref>). Hypertension was observed in 69.5% of the patients in this study, a similar percentage to that found in the CONAREC XII registry (<xref ref-type="bibr" rid="B27">Perna et&#xa0;al., 2015</xref>; <xref ref-type="bibr" rid="B1">Assun&#xe7;&#xe3;o et&#xa0;al., 2016</xref>), where 69.3% had heart failure. Diabetes was recorded in 20.9% of patients, slightly lower than that found by RETIC (<xref ref-type="bibr" rid="B16">Instituto Nacional de Estad&#xed;stica y Censos - I.N.D.E.C, 2019</xref>). Population studies (<xref ref-type="bibr" rid="B24">Men&#xe9;ndez et&#xa0;al., 2006</xref>; <xref ref-type="bibr" rid="B35">Slimel et al., 2010</xref>; <xref ref-type="bibr" rid="B5">Corradi et&#xa0;al., 2012</xref>) report values lower than those found here, probably due to a selection bias, given the characteristics of the cohort.</p>
<p>Heart failure was diagnosed in 36.0% of the cohort, which is expected in this population (<xref ref-type="bibr" rid="B10">Delucchi et&#xa0;al., 2017</xref>); 21.4% of the patients were classified as Kuschnir Grade 3 and 30.6% of this group required at least one hospitalization in the last year. The classification allows for an estimate of the severity of myocardial compromise and, consequently, the need for medical attention. If carried out adequately, this will improve quality of life and reduce costs of care.</p>
<p>The WHO estimates that more than 376,000 people in Argentina require medical attention due to ChD in health institutions across the country and particularly in patients with CMP associated with <italic>T. cruzi</italic> infection (Chagas disease in Latin America: an epidemiological update based on 2010 estimates). In Argentina, national guidelines (<xref ref-type="bibr" rid="B13">Enfermedades Infecciosas, 2018</xref>) establish that every infected person in the chronic stage of the disease must have at least an electrocardiogram exam, chest X-ray, and/or electrocardiogram study, as well as an annual evaluation of their health status. Surprisingly, in this study cohort, half of the patients with Ch-CMP were not evaluated according to the minimum requirements established by the guidelines based on the scientific consensus. Non-compliance with the guidelines, which makes it possible to establish functional capacity, and the possible risk, which makes it possible to schedule medical care adjusted to the person's need, indicates a low quality of care.caring for patients with Ch-CMP</p>
<p>In cases with pathological evidence, different scientific societies (<xref ref-type="bibr" rid="B36">Sociedad Argentina de Cardiolog&#x131;&#x301;&#xe1;, 2019</xref>; <xref ref-type="bibr" rid="B37">Sociedad Sudamericana de Cardiolog&#x131;&#x301;|&#xe1;, 2019</xref>) recommend performing other cardiological studies that evaluate the degree of cardiac structural compromise and functional capacity.</p>
<p>One of the strengths of this study is its comprehensive national coverage, given the participation of professionals from various regions of the country, and therefore &#x201c;real-life&#x201d; evidence was obtained. The low proportion of recommended diagnostic tests and treatments recommended to patients with myocardial compromise demonstrates the low adherence to expert recommendations.</p>
</sec>
<sec id="s5" sec-type="conclusion">
<label>5</label>
<title>Conclusion</title>
<p>The current study of individuals infected with <italic>T. cruzi</italic> and presenting with associated cardiomyopathy and other related comorbidities shows similar results to those found in other studies. With the objective of determining the medical practices performed on these types of patients, we found that Ch-CMP receives insufficient and inadequate care from public and private health systems, which are non-compliant with national guidelines (<xref ref-type="bibr" rid="B36">Sociedad Argentina de Cardiolog&#x131;&#x301;&#xe1;, 2019</xref>; <xref ref-type="bibr" rid="B37">Sociedad Sudamericana de Cardiolog&#x131;&#x301;|&#xe1;, 2019</xref>; <xref ref-type="bibr" rid="B13">Enfermedades Infecciosas, 2018</xref>) and the scientific consensus.</p>
<p>It is crucial to continue to amplify the study network; promote educational programs for data registry, collection, and analysis; and urgently address the suboptimal medical attention received by those with Ch-CMP by aiming for better compliance with and access to the healthcare practices and interventions established by evidence-based recommendations.</p>
<p>Our study is subject to limitations, mainly because it is a retrospective descriptive study using secondary data that may lack quality and completeness. In many of the complementary studies we did not have access to the original records, only transcribed reports in the medical records. In addition, we cannot ensure that the study sample is representative of the population of patients with CD in Argentina since it was not randomly selected and was limited only to the data collected in the centers that participate in the network of professionals coordinated by the Institute of Epidemiological Investigations of the National Academy of Medicine of Buenos Aires. Having established this, we consider that the information provided allows us to believe that a better quality of care for patients with Ch-CMP is necessary, as is improving the education and communication skills of health teams and ensuring adequate access to medical care for patients with Ch-CMP.</p>
<p>Further studies are ongoing using our database, and we hope that results might provide more detailed information on this population.</p>
</sec>
<sec id="s6" sec-type="data-availability">
<title>Data availability statement</title>
<p>The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.</p>
</sec>
<sec id="s7" sec-type="ethics-statement">
<title>Ethics statement</title>
<p>This study respected ethical principles and current regulatory norms; it was approved by the ethical committee of the National Academy of Medicine (Act 12906/18/E). The participation of the professionals was voluntary and expressed through digital informed consent. Data were extracted from the clinical history of the patients by the professionals in an anonymous manner and automatically coded without temporal relation to the medical attention or analysis. The data were registered in a specifically designed web form that did not require the input of personal data. The inclusion of data did not imply, in any case, the modification of clinical conduct since there was no temporal relation.</p>
</sec>
<sec id="s8" sec-type="author-contributions">
<title>Author contributions</title>
<p>The data were collected and the manuscripts was written, read, and approved by all authors.</p>
</sec>
</body>
<back>
<sec id="s9" sec-type="funding-information">
<title>Funding</title>
<p>This study received partial funding from Novartis. The funder was not involved in the study design, collection, analysis, the interpretation of data, the writing of this article, or the decision to submit it for publication. All authors declare no other competing interests.</p>
</sec>
<ack>
<title>Acknowledgments</title>
<p>We would like to acknowledge the contribution of the medical professionals that contributed their patient data and Maria Victoria Periago of CONICET/Fundaci&#xf3;n Mundo Sano for her assistance in the final editing of this article.</p>
</ack>
<sec id="s10" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
<p>The authors declare that this study received partial funding from Novartis. The funder was not involved in the study design, collection, analysis, the interpretation of data, the writing of this article, or the decision to submit it for publication.</p>
<p>The author RC declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.</p>
</sec>
<sec id="s11" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<ref-list>
<title>References</title>
<ref id="B1">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Assun&#xe7;&#xe3;o</surname> <given-names>A. N.</given-names>
<suffix>Jr</suffix>
</name>
<name>
<surname>Jerosch-Herold</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Melo</surname> <given-names>R. L.</given-names>
</name>
<name>
<surname>Mauricio</surname> <given-names>A. V.</given-names>
</name>
<name>
<surname>Rocha</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Torre&#xe3;o</surname> <given-names>J. A.</given-names>
</name>
<etal/>
</person-group>. (<year>2016</year>). <article-title>Chagas' heart disease: gender differences in myocardial damage assessed by cardiovascular magnetic resonance</article-title>. <source>J. Cardiovasc. Magn. Reson.</source> <volume>18</volume> (<issue>1</issue>), <fpage>88</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s12968-016-0307-5</pub-id>
</citation>
</ref>
<ref id="B2">
<citation citation-type="journal">(<year>2015</year>). <article-title>Chagas disease in Latin America: an epidemiological update based on 2010 estimates</article-title>. <source>Wkly Epidemiol. Rec</source> <volume>90</volume> (<issue>6</issue>), <fpage>33</fpage>&#x2013;<lpage>43</lpage>.</citation>
</ref>
<ref id="B3">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Bellotti</surname> <given-names>G.</given-names>
</name>
<name>
<surname>Bocchi</surname> <given-names>E. A.</given-names>
</name>
<name>
<surname>De Moraes</surname> <given-names>A. V.</given-names>
</name>
<name>
<surname>Higuchi</surname> <given-names>M. L.</given-names>
</name>
<name>
<surname>Barbero-Marcial</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Sosa</surname> <given-names>E.</given-names>
</name>
<etal/>
</person-group>. (<year>1996</year>). <article-title>
<italic>In vivo</italic> detection of trypanosoma cruzi antigens in hearts of patients with chronic chagas' heart disease</article-title>. <source>Am. Heart J.</source> <volume>131</volume>, <fpage>301</fpage>&#x2013;<lpage>307</lpage>. doi: <pub-id pub-id-type="doi">10.1016/S0002-8703(96)90358-0</pub-id>
</citation>
</ref>
<ref id="B4">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Biolo</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Ribeiro</surname> <given-names>A. L.</given-names>
</name>
<name>
<surname>Clausell</surname> <given-names>N.</given-names>
</name>
</person-group> (<year>2010</year>). <article-title>Chagas cardiomyopathy&#x2013;where do we stand after a hundred years</article-title>? <source>Prog. Cardiovasc. Dis.</source> <volume>52</volume>, <fpage>300</fpage>&#x2013;<lpage>316</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.pcad.2009.11.008</pub-id>
</citation>
</ref>
<ref id="B5">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Corradi</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Colque</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Perez</surname> <given-names>G.</given-names>
</name>
<name>
<surname>Costabel</surname> <given-names>J. P.</given-names>
</name>
<name>
<surname>Da Rosa</surname> <given-names>W.</given-names>
</name>
</person-group> (<year>2012</year>). <article-title>Registro CONAREC XVIII - insuficiencia card&#xed;aca</article-title>. <source>Rev. Fed Arg Cardiol.</source> <volume>41</volume> (<issue>Supl. 1</issue>), <fpage>11</fpage>.</citation>
</ref>
<ref id="B6">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Coura</surname> <given-names>J. R.</given-names>
</name>
<name>
<surname>Borges-Pereira</surname> <given-names>J.</given-names>
</name>
</person-group> (<year>2010</year>). <article-title>Chagas disease: 100 years after its discovery. a systematic review</article-title>. <source>Acta Trop.</source> <volume>115</volume>, <fpage>5</fpage>&#x2013;<lpage>13</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.actatropica.2010.03.008</pub-id>
</citation>
</ref>
<ref id="B7">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Cucunub&#xe1;</surname> <given-names>Z. M.</given-names>
</name>
<name>
<surname>Manne-Goehler</surname> <given-names>J. M.</given-names>
</name>
<name>
<surname>D&#xed;az</surname> <given-names>D.</given-names>
</name>
<name>
<surname>Nouvellet</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Bernal</surname> <given-names>O.</given-names>
</name>
<name>
<surname>Marchiol</surname> <given-names>A.</given-names>
</name>
<etal/>
</person-group>. (<year>2017</year>). <article-title>How universal is coverage and access to diagnosis and treatment for chagas disease in Colombia? a health systems analysis</article-title>. <source>Soc. Sci. Med.</source> <volume>175</volume>, <fpage>187</fpage>&#x2013;<lpage>198</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.socscimed.2017.01.002</pub-id>
</citation>
</ref>
<ref id="B8">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Cutshaw</surname> <given-names>M. K.</given-names>
</name>
<name>
<surname>Sciaudone</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Bowman</surname> <given-names>N. M.</given-names>
</name>
</person-group> (<year>2023</year>). <article-title>Risk factors for progression to chronic chagas cardiomyopathy: a systematic review and meta-analysis</article-title>. <source>Am. J. Trop. Med. Hyg</source>, <fpage>1</fpage>&#x2013;<lpage>11</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.4269/ajtmh.22-0630</pub-id>
</citation>
</ref>
<ref id="B9">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>D&#xe1;vila-Spinetti</surname> <given-names>D. F.</given-names>
</name>
<name>
<surname>Colmenarez-Mendoza</surname> <given-names>H. L.</given-names>
</name>
<name>
<surname>Lobo-Vielma</surname> <given-names>L.</given-names>
</name>
</person-group> (<year>2005</year>). <article-title>Mecanismos causantes de la progresi&#xf3;n del da&#xf1;o mioc&#xe1;rdico en la enfermedad de chagas cr&#xf3;nica</article-title>. <source>Rev. Esp Cardiol.</source> <volume>58</volume>, <fpage>1007</fpage>&#x2013;<lpage>1009</lpage>. doi: <pub-id pub-id-type="doi">10.1157/13078546</pub-id>
</citation>
</ref>
<ref id="B10">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Delucchi</surname> <given-names>A. M.</given-names>
</name>
<name>
<surname>Majul</surname> <given-names>C. R.</given-names>
</name>
<name>
<surname>Vicario</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Cerezo</surname> <given-names>G. H.</given-names>
</name>
<name>
<surname>F&#xe1;bregues</surname> <given-names>G.</given-names>
</name>
<collab>por los investigadores del 2&#xb0; registro nacional de hipertensi&#xf3;n arterial (RENATA 2)</collab>
</person-group> (<year>2017</year>). <article-title>National registry of hypertension. epidemiological characteristics of hypertension in argentina. the RENATA 2 study</article-title>. <source>Rev. Argen Cardiol.</source> <volume>85</volume> (<issue>4</issue>), <fpage>1</fpage>&#x2013;<lpage>8</lpage>.</citation>
</ref>
<ref id="B11">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Echalar</surname> <given-names>J. C.</given-names>
</name>
<name>
<surname>Veliz</surname> <given-names>D.</given-names>
</name>
<name>
<surname>Urquizo</surname> <given-names>H. N.</given-names>
</name>
<name>
<surname>Niemeyer</surname> <given-names>H. M.</given-names>
</name>
<name>
<surname>Pinto</surname> <given-names>C. F.</given-names>
</name>
</person-group> (<year>2021</year>). <article-title>Age-related anomalies of electrocardiograms in patients from areas with differential seroprevalence of chagas disease in southern Bolivia</article-title>. <source>Parasite Epidemiol. Control</source> <volume>13</volume>, <fpage>1</fpage>&#x2013;<lpage>8</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.parepi.2021.e00204</pub-id>
</citation>
</ref>
<ref id="B12">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Elizari</surname> <given-names>M. V.</given-names>
</name>
</person-group> (<year>1999</year>). <article-title>La miocardiopat&#xed;a chag&#xe1;sica. perspectiva hist&#xf3;rica</article-title>. <source>Med (Buenos Aires)</source> <volume>59</volume> (<issue>Supl.II</issue>), <fpage>25</fpage>&#x2013;<lpage>40</lpage>.</citation>
</ref>
<ref id="B13">
<citation citation-type="web">
<person-group person-group-type="author">
<collab>Enfermedades Infecciosas</collab>
</person-group> (<year>2018</year>) <source>Chagas. atenci&#xf3;n del paciente infectado con trypanosoma cruzi. guias para el equipo de salud. ministerios de salud y desarrollo social. Argentina</source>. Available at: <uri xlink:href="https://bancos.salud.gob.ar/sites/default/files/2020-01/chagas-atencion-paciente-infectado-2018.pdf">https://bancos.salud.gob.ar/sites/default/files/2020-01/chagas-atencion-paciente-infectado-2018.pdf</uri>.</citation>
</ref>
<ref id="B14">
<citation citation-type="book">
<person-group person-group-type="author">
<name>
<surname>Fanjul</surname> <given-names>G.</given-names>
</name>
<name>
<surname>Gascon</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Moriana</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Rubio</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Sarukhan</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Solano</surname> <given-names>M.</given-names>
</name>
</person-group> (<year>2016</year>). &#x201c;<article-title>Equipo de an&#xe1;lisis isglobal</article-title>,&#x201d; in <source>Chagas: 5 problemas y una serie de soluciones</source> (<publisher-loc>Barcelona, Spain</publisher-loc>: <publisher-name>IS Global. Instituto de Salud Global</publisher-name>). Available at: <uri xlink:href="https://www.isglobal.org/enfermedad-de-chagas">https://www.isglobal.org/enfermedad-de-chagas</uri>.</citation>
</ref>
<ref id="B15">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Freitas Lidani</surname> <given-names>K. C.</given-names>
</name>
<name>
<surname>Sandri</surname> <given-names>T. L.</given-names>
</name>
<name>
<surname>Castillo-Neyra</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Antunes Andrade</surname> <given-names>F.</given-names>
</name>
<name>
<surname>Guimar&#xe3;es</surname> <given-names>C. M.</given-names>
</name>
<name>
<surname>Marques</surname> <given-names>E. N.</given-names>
</name>
<etal/>
</person-group>. (<year>2020</year>). <article-title>Clinical and epidemiological aspects of chronic chagas disease from southern Brazil</article-title>. <source>Rev. Da Sociedade Bras. Med Trop.</source> <volume>53</volume>, <elocation-id>e20200225</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1590/0037-8682-0225-2020</pub-id>
</citation>
</ref>
<ref id="B16">
<citation citation-type="book">
<person-group person-group-type="author">
<collab>Instituto Nacional de Estad&#xed;stica y Censos - I.N.D.E.C</collab>
</person-group> (<year>2019</year>). &#x201c;<article-title>4&#xb0; encuesta nacional de factores de riesgo. resultados definitivos. - 1a ed.</article-title>,&#x201d; (<publisher-name>Ciudad Auto&#x301;&#x144;oma de Buenos Aires: Instituto Nacional de Estad&#xed;stica y Censos &#x2013; INDEC; Secretar&#x131;&#x301;&#xe1; de Gobierno de Salud de la Nacio&#x301;&#x144;</publisher-name>). Available at: <uri xlink:href="https://www.indec.gob.ar/ftp/cuadros/publicaciones/enfr_2018_resultados_definitivos.pdf">https://www.indec.gob.ar/ftp/cuadros/publicaciones/enfr_2018_resultados_definitivos.pdf</uri>.</citation>
</ref>
<ref id="B17">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kuschnir</surname> <given-names>E.</given-names>
</name>
<name>
<surname>Sgammini</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Castro</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Evequoz</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Ledesma</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Brunetto</surname> <given-names>J.</given-names>
</name>
</person-group> (<year>1985</year>). <article-title>Evaluation of cardiac function by radioisotopic angiography in patients with chronic chagas cardiopathy</article-title>. <source>Arq Bras. Cardiol.</source> <volume>45</volume>, <fpage>249</fpage>&#x2013;<lpage>256</lpage>.</citation>
</ref>
<ref id="B18">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Manzullo</surname> <given-names>E. C.</given-names>
</name>
<name>
<surname>Chuit</surname> <given-names>R.</given-names>
</name>
</person-group> (<year>1999</year>). <article-title>Risk of death due to chronic chagasic cardiopathy</article-title>. <source>Mem Inst Oswaldo Cruz</source> <volume>94</volume> (<supplement>Suppl. I</supplement>), <fpage>317</fpage>&#x2013;<lpage>320</lpage>. Rio de Janeiro. doi: <pub-id pub-id-type="doi">10.1590/S0074-02761999000700060</pub-id>
</citation>
</ref>
<ref id="B19">
<citation citation-type="book">
<person-group person-group-type="author">
<name>
<surname>Mar&#xed;n-Neto</surname> <given-names>J. A.</given-names>
</name>
<name>
<surname>Rassi</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Rassi</surname> <given-names>A.</given-names>
</name>
</person-group> (<year>2015</year>). &#x201c;<article-title>Pathogenesis and prognostic factors in chronic chagas cardiomyopathy</article-title>,&#x201d; in <source>XI taller sobre la enfermedad de chagas</source> (<publisher-loc>Barcelona, Spain</publisher-loc>: <publisher-name>Rev Esp Salud P&#xfa;blica</publisher-name>), <fpage>8</fpage>&#x2013;<lpage>21</lpage>.</citation>
</ref>
<ref id="B20">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Marin Neto</surname> <given-names>J. A.</given-names>
</name>
<name>
<surname>Sim&#xf5;es</surname> <given-names>M. V.</given-names>
</name>
<name>
<surname>Rassi</surname> <given-names>A.</given-names>
</name>
</person-group> (<year>2013</year>). <article-title>Pathogenesis of chronic chagas cardiomyopathy: the role of coronary microvascular derangements</article-title>. <source>Rev. Soc. Bras. Med. Trop.</source> <volume>46</volume> (<issue>5</issue>), <fpage>536</fpage>&#x2013;<lpage>541</lpage>. doi: <pub-id pub-id-type="doi">10.1590/0037-8682-0028-2013</pub-id>
</citation>
</ref>
<ref id="B21">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Martins-Melo</surname> <given-names>F. R.</given-names>
</name>
<name>
<surname>Heukelbach</surname> <given-names>J.</given-names>
</name>
</person-group> (<year>2013</year>). <article-title>Epidemiology and spatial distribution of mortality related to chagas disease in Brazil, 1999 to 2007</article-title>. <source>Cad Saude Col</source> <volume>21</volume>, <fpage>105</fpage>&#x2013;<lpage>106</lpage>. doi: <pub-id pub-id-type="doi">10.1590/S1414-462X2013000100017</pub-id>
</citation>
</ref>
<ref id="B22">
<citation citation-type="book">
<person-group person-group-type="author">
<name>
<surname>Mazza</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Jorg</surname> <given-names>M. E.</given-names>
</name>
</person-group> (<year>1936</year>). <article-title>Novena reuni&#xf3;n de la Sociedad Argentina de Patologia Regional del filiales y afiliadas: Mendoza 1, 2, 3 y 4 de octubre de 1935, en homenaje a la memoria de Carlos Chagas, Volume 1 (Imprenta de la Universidad)</article-title>.</citation>
</ref>
<ref id="B23">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Medina-Rinc&#xf3;n</surname> <given-names>G. J.</given-names>
</name>
<name>
<surname>Gallo-Bernal</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Jim&#xe9;nez</surname> <given-names>P. A.</given-names>
</name>
<name>
<surname>Cruz-Saavedra</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Ram&#xed;rez</surname> <given-names>J. D.</given-names>
</name>
<name>
<surname>Rodr&#xed;guez</surname> <given-names>M. J.</given-names>
</name>
<etal/>
</person-group>. (<year>2021</year>). <article-title>Molecular and clinical aspects of chronic manifestations in chagas disease: a state-of-the-Art review</article-title>. <source>Pathogens</source> <volume>10</volume> (<issue>11</issue>), <elocation-id>1493</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/pathogens10111493</pub-id>
</citation>
</ref>
<ref id="B24">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Men&#xe9;ndez</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Lobo M&#xe1;rquez</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Perna</surname> <given-names>E. R.</given-names>
</name>
</person-group> (<year>2006</year>). <article-title>Registro tucumano de insuficiencia cardiaca (RETIC)</article-title>. <source>Resultados Finales Rev. Fed Arg Cardiol.</source> <volume>35</volume> (<issue>Supl. 1</issue>), <fpage>55</fpage>.</citation>
</ref>
<ref id="B25">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Nunes</surname> <given-names>M. C. P.</given-names>
</name>
<name>
<surname>Beaton</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Acquatella</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Bern</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Bolger</surname> <given-names>A. F.</given-names>
</name>
<name>
<surname>Echeverr&#xed;a</surname> <given-names>L. E.</given-names>
</name>
<etal/>
</person-group>. (<year>2018</year>). <article-title>American Heart association rheumatic fever, endocarditis and Kawasaki disease committee of the council on cardiovascular disease in the young; council on cardiovascular and stroke nursing; and stroke council. chagas cardiomyopathy: an update of current clinical knowledge and management: a scientific statement from the American heart association</article-title>. <source>Circulation</source> <volume>138</volume> (<issue>12</issue>), <fpage>e169</fpage>&#x2013;<lpage>e209</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1161/CIR.0000000000000599</pub-id>
</citation>
</ref>
<ref id="B26">
<citation citation-type="book">
<person-group person-group-type="author">
<collab>Pan American Health Organization</collab>
</person-group> (<year>2019</year>). <source>Guidelines for the diagnosis and treatment of chagas disease</source> (<publisher-loc>Washington, D.C.</publisher-loc>: <publisher-name>Publications of the Pan American Health Organization</publisher-name>). Available at: <uri xlink:href="http://iris.paho.org">http://iris.paho.org</uri>.</citation>
</ref>
<ref id="B27">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Perna</surname> <given-names>E. R.</given-names>
</name>
<name>
<surname>Coronel</surname> <given-names>M. L.</given-names>
</name>
<name>
<surname>C&#xed;mbaro Canella</surname> <given-names>J. P.</given-names>
</name>
<name>
<surname>Echazarreta</surname> <given-names>D.</given-names>
</name>
</person-group> (<year>2015</year>). <article-title>Revisi&#xf3;n de insuficiencia card&#xed;aca en Argentina avances y retrocesos luego de dos d&#xe9;cadas de registros y m&#xe1;s de 19000 pacientes incluidos</article-title>. <source>Insuf Card</source> <volume>10</volume> (<issue>1</issue>), <fpage>2</fpage>&#x2013;<lpage>10</lpage>.</citation>
</ref>
<ref id="B28">
<citation citation-type="book">
<person-group person-group-type="author">
<name>
<surname>Pinto Dias</surname> <given-names>J. C.</given-names>
</name>
</person-group> (<year>1982</year>). <source>Doen&#xe7;a de Chagas en Bamb&#xfa;i, Minas Gerais, Brasil. estudo cl&#xed;nico epidemiol&#xf3;gico a partir da fase aguda entre 1940 e 1982 / Chagas disease in Bambu&#xed;, Minas Gerais, Brazil: clinical, epidemiological study from the acute phase, between 1940 and 1982</source> (<publisher-loc>Belo Horizonte, Brazil</publisher-loc>: <publisher-name>Universidade Federal de Minas Gerais</publisher-name>).</citation>
</ref>
<ref id="B29">
<citation citation-type="book">
<person-group person-group-type="author">
<name>
<surname>Pinto Dias</surname> <given-names>J. C.</given-names>
</name>
</person-group> (<year>1985</year>). &#x201c;<article-title>Hist&#xf3;ria natural da cardiopatia chag&#xe1;sica</article-title>,&#x201d; in <source>Cardiopatia chag&#xe1;sica</source>. Eds. <person-group person-group-type="editor">
<name>
<surname>Can&#xe7;ado</surname> <given-names>J. R.</given-names>
</name>
<name>
<surname>Chuster</surname> <given-names>M.</given-names>
</name>
</person-group>(<publisher-loc>Belo Horizonte, MG, Brazil: Funda&#xe7;&#xe3;o Carlos Chagas</publisher-loc>), <fpage>99</fpage>&#x2013;<lpage>113</lpage>.</citation>
</ref>
<ref id="B30">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Rassi</surname> <given-names>A. J.</given-names>
</name>
<name>
<surname>Rassi</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Marin-Neto</surname> <given-names>A.</given-names>
</name>
</person-group> (<year>2010</year>). <article-title>Chagas disease</article-title>. <source>Lancet</source> <volume>375</volume>, <fpage>1388</fpage>&#x2013;<lpage>1402</lpage>. doi: <pub-id pub-id-type="doi">10.1016/S0140-6736(10)60061-X</pub-id>
</citation>
</ref>
<ref id="B31">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ribeiro</surname> <given-names>A. L.</given-names>
</name>
<name>
<surname>Nunes</surname> <given-names>M. P.</given-names>
</name>
<name>
<surname>Teixeira</surname> <given-names>M. M.</given-names>
</name>
<name>
<surname>Rocha</surname> <given-names>M. O.</given-names>
</name>
</person-group> (<year>2012</year>). <article-title>Diagnosis and management of chagas disease and cardiomyopathy</article-title>. <source>Nat. Rev. Cardiol.</source> <volume>9</volume> (<issue>10</issue>), <fpage>576</fpage>&#x2013;<lpage>589</lpage>. doi: <pub-id pub-id-type="doi">10.1038/nrcardio.2012.109</pub-id>
</citation>
</ref>
<ref id="B32">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Rosa-Jim&#xe9;nez</surname> <given-names>F.</given-names>
</name>
<name>
<surname>Montijano Cabrera</surname> <given-names>A. M.</given-names>
</name>
<name>
<surname>Herr&#xe1;iz Montalvo</surname> <given-names>C. I.</given-names>
</name>
<name>
<surname>Zambrana Garc&#xed;a</surname> <given-names>J. L.</given-names>
</name>
</person-group> (<year>2005</year>). <article-title>&#xbf;Solicitan las mujeres m&#xe1;s consultas al &#xe1;rea m&#xe9;dica que los hombres</article-title>? <source>Med. Interna (Madrid)</source> <volume>22</volume> (<issue>11</issue>), <fpage>515</fpage>&#x2013;<lpage>519</lpage>.</citation>
</ref>
<ref id="B33">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Rosenbaum</surname> <given-names>M. B.</given-names>
</name>
</person-group> (<year>1964</year>). <article-title>Chagasic cardiomyopathy</article-title>. <source>Prog. Cardiovasc. Dis.</source> <volume>117</volume>, <fpage>188</fpage>&#x2013;<lpage>225</lpage>.</citation>
</ref>
<ref id="B34">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Schmunis</surname> <given-names>G. A.</given-names>
</name>
<name>
<surname>Yadon</surname> <given-names>Z. E.</given-names>
</name>
</person-group> (<year>2010</year>). <article-title>Chagas disease: a Latin American health problem becoming a world health problem</article-title>. <source>Acta Trop.</source> <volume>115</volume>, <fpage>14</fpage>&#x2013;<lpage>21</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.actatropica.2009.11.003</pub-id>
</citation>
</ref>
<ref id="B35">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Slimel</surname> <given-names>M. R.</given-names>
</name>
<name>
<surname>Mendoza</surname> <given-names>S. M.</given-names>
</name>
<name>
<surname>Tannuri</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Coppolillo</surname> <given-names>F. E.</given-names>
</name>
<name>
<surname>Masi</surname> <given-names>J. D.</given-names>
</name>
</person-group> (<year>2010</year>). <article-title>Epidemiolog&#xed;a de la diabetes en Argentina</article-title>. <source>Av Diabetol.</source> <volume>26</volume> (<issue>2</issue>), <fpage>101</fpage>&#x2013;<lpage>106</lpage>. doi: <pub-id pub-id-type="doi">10.1016/S1134-3230(10)62006-6</pub-id>
</citation>
</ref>
<ref id="B36">
<citation citation-type="web">
<person-group person-group-type="author">
<collab>Sociedad Argentina de Cardiolog&#xed;a</collab>
</person-group> (<year>2019</year>) <source>Consenso enfermedad de chagas</source>. Available at: <uri xlink:href="https://www.sac.org.ar/wp-content/uploads/2020/12/consenso-87-8.pdf">https://www.sac.org.ar/wp-content/uploads/2020/12/consenso-87-8.pdf</uri>.</citation>
</ref>
<ref id="B37">
<citation citation-type="web">
<person-group person-group-type="author">
<collab>Sociedad Sudamericana de Cardiolog&#xed;a</collab>
</person-group> (<year>2019</year>) <source>Acuerdo regional de los expertos en chagas de las sociedades de cardiolog&#xed;a sudamericanas</source>. Available at: <uri xlink:href="https://www.sscardio.org/5274-2/">https://www.sscardio.org/5274-2/</uri>.</citation>
</ref>
<ref id="B38">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Takle</surname> <given-names>G. B.</given-names>
</name>
<name>
<surname>Hudson</surname> <given-names>L.</given-names>
</name>
</person-group> (<year>1989</year>). <article-title>Autoimmunity and chagas' disease</article-title>. <source>Curr. Top. Microbiol. Immunol.</source> <volume>145</volume>, <fpage>79</fpage>&#x2013;<lpage>92</lpage>. doi: <pub-id pub-id-type="doi">10.1007/978-3-642-74594-2_7</pub-id>
</citation>
</ref>
<ref id="B39">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Viotti</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Vigliano</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Lococo</surname> <given-names>B.</given-names>
</name>
<name>
<surname>Bertocchi</surname> <given-names>G.</given-names>
</name>
<name>
<surname>Petti</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Alvarez</surname> <given-names>M. G.</given-names>
</name>
<etal/>
</person-group>. (<year>2006</year>). <article-title>Long-term cardiac outcomes of treating chronic chagas' disease with benznidazole versus no treatment: a nonrandomized trial</article-title>. <source>Ann. Internal Med.</source> <volume>144</volume>, <fpage>724</fpage>&#x2013;<lpage>734</lpage>. doi: <pub-id pub-id-type="doi">10.7326/0003-4819-144-10-200605160-00006</pub-id>
</citation>
</ref>
</ref-list>
</back>
</article>