<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "https://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.0" specific-use="sps-1.6" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">LXgzknC7rWcyrMH5NrXnHHL</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2017000600546</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20170074</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
          <subj-group>
            <subject>Pacemaker</subject>
          </subj-group>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Pacemaker Implants in Children and Adolescents with Chagas Disease in Brazil: 18-Year Incidence</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Mizzaci</surname>
            <given-names>Carolina Christianini</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Souza</surname>
            <given-names>Thiago Gon&#231;alves Schroder e</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Targueta</surname>
            <given-names>Gabriel Pelegrineti</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>T&#243;tora</surname>
            <given-names>Ana Paula Frederico</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mateos</surname>
            <given-names>Juan Carlos Pach&#243;n</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mateos</surname>
            <given-names>Jos&#233; Carlos Pachon</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <aff id="aff1">
          <institution content-type="orgname">Instituto Dante Pazzanese de Cardiologia</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brazil</institution>
          <institution content-type="normalized">Instituto Dante Pazzanese de Cardiologia</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Thiago Gon&#231;alves Schroder e Souza,</bold> Av. Dr. Dante Pazzanese, 500. Postal Code 04012-909, Ibirapuera, S&#227;o Paulo, SP - Brazil. E-mail: <email>thiagojfx@gmail.com</email>, <email>thiago.schroder@usp.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Mizzaci CC, Souza TGS, Mateos JCP, Mateos JCP; Acquisition of data: Mizzaci CC, Targueta GP, T&#243;tora APF; Analysis and interpretation of the data: Souza TGS, Targueta GP, T&#243;tora APF; Statistical analysis: Souza TGS; Writing of the manuscript: Mizzaci CC, Souza TGS, Targueta GP, T&#243;tora APF, Mateos JCP; Critical revision of the manuscript for intellectual content: Mizzaci CC, Mateos JCP, Mateos JCP.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub-ppub">
        <month>06</month>
        <year>2017</year>
      </pub-date>
      <volume>108</volume>
      <issue>6</issue>
      <fpage>546</fpage>
      <lpage>551</lpage>
      <history>
        <date date-type="received">
          <day>15</day>
          <month>06</month>
          <year>2016</year>
        </date>
        <date date-type="rev-recd">
          <day>13</day>
          <month>10</month>
          <year>2016</year>
        </date>
        <date date-type="accepted">
          <day>30</day>
          <month>12</month>
          <year>2016</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>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 work is properly cited.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Chagas disease continues to be a serious public health problem, and accounts for 25-30% of the indications for cardiac stimulation in Brazil.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To assess clinical and epidemiological characteristics of patients with Chagas disease, younger than 18 years, who had undergone pacemaker implantation in Brazil between 1994 and 2011, and its temporal trend.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>This was a cross-sectional analysis of data from the Brazilian Pacemaker Registry database. The following variables were analyzed: year when pacemaker was implanted, location, age, sex, ethnic group, functional class and the main electrocardiographic findings at baseline.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>In a total of 183,123 implants performed between 1994 and 2011, 214 implants of cardiac stimulation device in Chagas disease patients aged younger than 18 years were identified. Mean age at implantation was 5.6 &#177; 6.2 years. Second- and third-degree atrioventricular blocks corresponded to 71% of indications for pacemaker implantation. Fifty-six percent of the procedures were performed in the southeast region. Regarding the total number of pacemaker implants per year, there was a remarkable increase in the implants for all causes. However, time series analysis of the implants in Chagas disease patients younger than 18 years revealed a significant reduction in the annual number of implants<bold>.</bold></p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>There has been an important reduction in the number of pacemaker implantations among children and adolescents with Chagas disease, suggesting a reduction in the vertical transmission of the parasite.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Retrospective Studies</kwd>
        <kwd>Pacemaker,Artificial</kwd>
        <kwd>Child</kwd>
        <kwd>Adolescents</kwd>
        <kwd>Chagas Disease</kwd>
        <kwd>Chagas Cardiomyopathy</kwd>
        <kwd>Epidemiology</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Endemic in South America and emerging in Europe and in the United States, Chagas disease continues to be a serious public health problem. Estimates indicate that there are 2.9 - 7.2 million people with Chagas disease in Brazil,<xref ref-type="bibr" rid="B1">1</xref> which accounts for approximately 6 thousand deaths per year.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref> According to the Brazilian Pacemaker Registry (BPR), 25%-30% of cardiac stimulation are performed for Chagas disease in Brazil.<xref ref-type="bibr" rid="B4">4</xref>
			</p>
      <p>In addition to transmission via infected feces of the hematophagous triatomine insect, Trypanosoma cruzi may also be transmitted by blood transfusion, consumption of contaminated food or drinks, and congenital transmission (from mother to child).<xref ref-type="bibr" rid="B5">5</xref> Due to a more effective control of both vector and transfusional transmission, congenital route has emerged as the most important way of transmission in most endemic areas.<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B7">7</xref>
			</p>
      <p>Prevalence of <italic>T.cruzi</italic> infection in pregnancy varies from 1% to 40%,<xref ref-type="bibr" rid="B8">8</xref><sup>-</sup><xref ref-type="bibr" rid="B12">12</xref> and congenital transmission may reach 28.6%.<xref ref-type="bibr" rid="B7">7</xref> Recent estimates indicate that annually, more than 14 thousand babies are born with congenital Chagas disease in Latin America. A Brazilian study conducted between 2001 and 2008 on 105 thousand children aged from 0 to 5 years living in rural areas reported a 0.03% prevalence of <italic>T. cruzi,</italic> 0.02% for probable congenital transmission and 0.01% for vectorial transmission.<xref ref-type="bibr" rid="B13">13</xref>
			</p>
      <p>Although most cases of congenital infection of <italic>T.cruzi</italic> are asymptomatic, it may cause premature death, low birth weight, stillbirths and clinical manifestations of Chagas disease at birth.<xref ref-type="bibr" rid="B14">14</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref> Since congenital transmission cannot be prevented, early diagnosis and treatment of congenital cases are the main goals of the programs for Chagas disease control.<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref>
			</p>
      <p>Considering changes in demography and transmission pathways, in particular the rising importance of vertical transmission, information on how these changes may affect patients&#8217; treatment and outcome are still scarce. Therefore, aiming to contribute to the knowledge on the theme, the objective of this study was to evaluate clinical and epidemiological characteristics of Chagas disease patients younger than 18 years, who had undergone a permanent pacemaker implantation in Brazil in the period between 1994 and 2011.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>Data of the BPR database were analyzed in this study. This database system, officially created by the Ministry of Health decree no. 41, of December 17<sup>th</sup>, 1994, is maintained by the Department of Artificial Cardiac Stimulation of the Brazilian Society of Cardiology Surgery. The system holds information of permanent cardiac stimulation procedures performed in Brazil by means of a standardized, specific form about generator implants performed in the country. Completed forms were forwarded to the central, where the information was registered.</p>
      <p>The following variables were analyzed: year when implant was performed, place of origin, age, sex, ethnic group, heart failure functional class according to the New York Heart Association (NYHA) criteria, and the main electrocardiographic finding that indicated the need for a pacemaker.</p>
      <p>Categorical variables were expressed as absolute and relative frequencies, and continuous variables as mean and standard deviation. Statistical analysis was performed using the SPSS (<italic>Statistical Package for the Social Sciences</italic>) software.</p>
      <p>Temporal variation in the number of pacemaker implants was assessed by the Jonckheere&#8217;s trend test, and the alpha error was set at 0.05.</p>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>Between 1994 and 2011, a total of 183,123 patients undergoing first pacemaker implantation were identified. Of this total, 35,204 were performed in patients with Chagas disease, and 214 of them consisted of surgical implantation of cardiac stimulation devices in patients aged 17 years or less.</p>
      <p>In the group of patients with Chagas disease younger than 18 years, who had undergone a pacemaker implant, mean age at procedure was 5.6 &#177; 6.2 years. Forty-five percent of these patients were women (5.2 &#177; 5.8 years), and 55% were men (6.1 &#177; 6.5 years). The <xref ref-type="fig" rid="f1">Figure 1</xref> shows the absolute frequency of implants performed per year throughout the period assessed (18 years), with a remarkable reduction in the number of implants. Mean number of implants was 20.6 implants/year in the first triennium (1994-1996), and 4.3 implants/year in the last triennium, indicating a 79.1% decrease between these periods.</p>
      <p>
        <fig id="f1">
          <label>Figure 1</label>
          <caption>
            <title>Annual distribution of pacemaker implantations in Chagas disease patients younger than 18 years.</title>
          </caption>
          <attrib>Source: Brazilian Pacemaker Registry.</attrib>
          <graphic xlink:href="1678-4170-abc-108-06-0546-70074-gf01.jpg"/></fig>
      </p>
      <p>Distribution of procedures by geographic area revealed a considerable diversity. Most patients came from the southeast of Brazil; in fact, most of Chagas disease patients were from this region (55.6% of the cases), followed by the central west region (25.7% of the cases).</p>
      <p>Regarding ethnic characteristics of the patients, most of them were white (49.5% of the implants), followed by mestizos (21.1%) and black individuals (14%). With respect to symptoms, most patients were NYHA class III and IV. One hundred patients (46.7%) were symptomatic during moderate/little efforts and 68 (31.8%) had symptoms at rest (<xref ref-type="table" rid="t1">Table 1</xref>).</p>
      <table-wrap id="t1">
        <label>Table 1</label>
        <caption>
          <title>Baseline characteristics of Chagas disease patients younger than 18 years who had undergone implantation of cardiac stimulation devices between 1994 and 2011</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="33%"/>
            <col width="33%"/>
            <col width="33%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">Patients (n)</th>
              <th align="center">
							</th>
              <th align="center">214</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Age (years)</td>
              <td align="center">
							</td>
              <td align="center">5.62 &#177; 6.2</td>
            </tr>
            <tr>
              <td align="left" rowspan="2" valign="top">Sex</td>
              <td align="center">Male</td>
              <td align="center">118 (55.2%)</td>
            </tr>
            <tr>
              <td align="center">Female</td>
              <td align="center">96 (44.8%)</td>
            </tr>
            <tr>
              <td align="left" rowspan="9" valign="top">Federative unit of origin</td>
              <td align="center">Sao Paulo</td>
              <td align="center">59 (27.6%)</td>
            </tr>
            <tr>
              <td align="center">Minas Gerais</td>
              <td align="center">59 (27.6%)</td>
            </tr>
            <tr>
              <td align="center">Goias</td>
              <td align="center">36 (16.8%)</td>
            </tr>
            <tr>
              <td align="center">Distrito Federal</td>
              <td align="center">19 (8.9%)</td>
            </tr>
            <tr>
              <td align="center">Parana</td>
              <td align="center">13 (6.1%)</td>
            </tr>
            <tr>
              <td align="center">Bahia</td>
              <td align="center">8 (3.7%)</td>
            </tr>
            <tr>
              <td align="center">Alagoas</td>
              <td align="center">5 (2.3%)</td>
            </tr>
            <tr>
              <td align="center">Pernambuco</td>
              <td align="center">5 (2.3%)</td>
            </tr>
            <tr>
              <td align="center">Others</td>
              <td align="center">10 (4.7%)</td>
            </tr>
            <tr>
              <td align="left" rowspan="4" valign="top">Ethnic group</td>
              <td align="center">White</td>
              <td align="center">106 (49.5%)</td>
            </tr>
            <tr>
              <td align="center">Mestizo</td>
              <td align="center">43 (20.1%)</td>
            </tr>
            <tr>
              <td align="center">Black</td>
              <td align="center">30 (14.0%)</td>
            </tr>
            <tr>
              <td align="center">Not declared</td>
              <td align="center">35 (16.3%)</td>
            </tr>
            <tr>
              <td align="left" rowspan="5" valign="top">Symptoms</td>
              <td align="center">Asymptomatic</td>
              <td align="center">19 (8.9%)</td>
            </tr>
            <tr>
              <td align="center">Symptoms during great efforts</td>
              <td align="center">22 (10.3%)</td>
            </tr>
            <tr>
              <td align="center">Symptoms during light/moderate efforts</td>
              <td align="center">100 (46.7%)</td>
            </tr>
            <tr>
              <td align="center">Symptoms during rest</td>
              <td align="center">68 (31.8%)</td>
            </tr>
            <tr>
              <td align="center">Not declared</td>
              <td align="center">5 (2.3%)</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <p>Seventy-one percent of the electrocardiographic indications for implantation of cardiac stimulation system were second- and third-degree atrioventricular block (AVB). Most of them were complete AVB with a wide QRS complex (42% of incidence), whereas complete AVB with a narrow QRS complex was reported in 10% of patients (<xref ref-type="fig" rid="f2">Figure 2</xref>).</p>
      <p>
        <fig id="f2">
          <label>Figure 2</label>
          <caption>
            <title>Electrocardiographic fndings suggesting the need for pacemaker implantation in Chagas disease patients younger than 18 years. AVB: atrioventricular block; LBBB: left bundle branch block.</title>
          </caption>
          <attrib>Source: Brazilian Pacemaker Registry.</attrib>
          <graphic xlink:href="1678-4170-abc-108-06-0546-70074-gf02.jpg"/></fig>
      </p>
      <p>Considering the total number of pacemaker implants per year (<xref ref-type="fig" rid="f3">Figure 3</xref>), there was a relevant, statistically significant increase in the number of implants for all causes. Time series analysis of the number of implants in Chagas disease patients of all ages showed a slight, non-significant variation. The possibility that this variation has occurred by chance cannot be ruled out (p trend = 0.5). Nevertheless, time series analysis of the implants in Chagas disease patients younger than 18 years revealed a significant reduction in the number of implants through the years (p trend &lt; 0.001) (<xref ref-type="fig" rid="f1">Figures 1</xref> and <xref ref-type="fig" rid="f3">3</xref>).</p>
      <p>
        <fig id="f3">
          <label>Figure 3</label>
          <caption>
            <title>Comparative graph of total pacemaker implants for all causes performed in Brazil per year (diamonds), total number of pacemaker implants in Chagas disease patients (square) and total pacemaker implants in Chagas disease patients younger than 18 years (triangle). P value of variation trend in each series through the years.</title>
          </caption>
          <attrib>Source: Brazilian Pacemaker Registry.</attrib>
          <graphic xlink:href="1678-4170-abc-108-06-0546-70074-gf03.jpg"/></fig>
      </p>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>In 1999, the Pan-American Health Organization (PAHO) declared that Triatoma infestans, the vector insect of <italic>T. cruzi</italic>, had been completely eliminated from human dwellings in Brazil, Chile, Uruguay, and large portions of Argentina, Bolivia, and Paraguay.<xref ref-type="bibr" rid="B19">19</xref> Nevertheless, despite recent advances in the control of T.cruzi transmission, Chagas disease continues to be an important public health problem in Latin America, with an annual impact of 430,000 DALYS (Disability-Adjusted Life Years) in the region.<xref ref-type="bibr" rid="B18">18</xref> Two hypotheses may be raised from this fact: </p>
      <p>
        <list list-type="order">
          <list-item>
            <p>there have been continuous or increasing expenses on the treatment of chronic Chagas disease, particularly on patients with chronic Chagas cardiomyopathy (CCC), or</p>
          </list-item>
          <list-item>
            <p>the parasite transmission modes have not been effectively controlled yet, which causes concern regarding blood transfusion transmission and vertical transmission of <italic>T.cruzi</italic>.</p>
          </list-item>
        </list>
      </p>
      <p>Data of the Brazilian Pacemaker Registry reflect CCC morbidity and hence yield useful information. Approximately 20% of infected patients develop CCC, and are at high risk for AVB and cardiac sudden death.<xref ref-type="bibr" rid="B20">20</xref> Interestingly, here we describe that, despite the increase in the number of pacemaker implants in Brazil, the number of procedures performed in Chagas disease patients per year did not change in the same period. This reflects a relative reduction of CCC and increase of other causes - such as senile degeneration of the conduction system - as indications for artificial stimulation of the heart. This finding may be due to a more effective control of vectorial and transfusional transmission of Chagas disease, as well as to an increase in life expectancy in the Brazilian population.<xref ref-type="bibr" rid="B21">21</xref>
			</p>
      <p>Our most important finding was the drastic decrease in the use of artificial cardiac stimulation in individuals younger than 18 years, which may suggest a better control of Chagas disease transmission in Brazil in the last decades. As previously mentioned, this result may be partly explained by the control of the vector. However, the decrease in blood transfusion transmission in addition to the continuous, effective control of vertical transmission of <italic>T.cruzi</italic> may have also contributed to it. At the end of the eighties, screening of blood donors for <italic>T.cruzi</italic> infection became compulsory in Brazil and, before this measure was implemented, approximately 20,000 new cases of Chagas disease were attributable to transfusional transmission per year. Today, the estimated risk of contamination of blood components by <italic>T.cruzi</italic> may be lower than 1 in 1,000,000 of transfusions.<xref ref-type="bibr" rid="B21">21</xref>
			</p>
      <p>Although the relevance of vertical transmission of Chagas disease has increased since the control of other transmission modes of the disease in Brazil, there are no conclusive data about its real magnitude. According to a recent systematic review,<xref ref-type="bibr" rid="B1">1</xref> the infection prevalence among pregnant women varies from 0.1 to 8.5%, and the vertical transmission rate varies from 0 to 5.2%. The decrease in vertical transmission is also corroborated by the fact that conduction system diseases require years for its establishment, occurring in last stages of CCC.</p>
      <p>Another finding that deserves attention is the uneven geographical distribution of the number of pacemaker implants across the national territory, not following the regions of higher prevalence of CCC. In addition to the concentration of main public health services in the big cities, the lack of trained experts in artificial cardiac pacing in children could also lead to the concentration of these procedures in tertiary health centers in capitals like Sao Paulo.</p>
      <p>This study has some limitations inherent to the study design. First, accuracy of data may be affected by the inter-subject variability of individuals responsible for feeding the database. Second, the study only allows us to formulate causal hypothesis related to the management of Chagas disease in the last years, not only for the retrospective nature of the study, but also for the adoption of a variable that does not represent the whole. Despite these considerations, we believe that our study provide useful information for the planning of health systems.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>There has been an important reduction in the number of pacemaker implantations among children and adolescents in Brazil, suggesting a better control of Chagas disease transmission in Brazil in the last two decades and a reduction in the vertical transmission of the parasite.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This study is not associated with any thesis or dissertation work.</p>
      </fn>
    </fn-group>
    <ref-list>
      <title>References</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1 Martins-Melo FR, Lima MaS, Ramos AN, Alencar CH, Heukelbach J. Systematic review: Prevalence of Chagas disease in pregnant women and congenital transmission of Trypanosoma cruzi in Brazil: a systematic review and meta-analysis. Trop Med Int Health. 2014;19(8):943-57.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Martins-Melo</surname>
              <given-names>FR</given-names>
            </name>
            <name>
              <surname>Lima</surname>
              <given-names>MaS</given-names>
            </name>
            <name>
              <surname>Ramos</surname>
              <given-names>AN</given-names>
            </name>
            <name>
              <surname>Alencar</surname>
              <given-names>CH</given-names>
            </name>
            <name>
              <surname>Heukelbach</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Systematic review: Prevalence of Chagas disease in pregnant women and congenital transmission of Trypanosoma cruzi in Brazil: a systematic review and meta-analysis</article-title>
          <source>Trop Med Int Health</source>
          <year>2014</year>
          <volume>19</volume>
          <issue>8</issue>
          <fpage>943</fpage>
          <lpage>957</lpage>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2 Martins-Melo FR, Ramos AN, Alencar CH, Lange W, Heukelbach J. Mortality of Chagas' disease in Brazil: spatial patterns and definition of high-risk areas. Trop Med Int Health. 2012;17(9):1066-75.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Martins-Melo</surname>
              <given-names>FR</given-names>
            </name>
            <name>
              <surname>Ramos</surname>
              <given-names>AN</given-names>
            </name>
            <name>
              <surname>Alencar</surname>
              <given-names>CH</given-names>
            </name>
            <name>
              <surname>Lange</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Heukelbach</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Mortality of Chagas' disease in Brazil: spatial patterns and definition of high-risk areas</article-title>
          <source>Trop Med Int Health</source>
          <year>2012</year>
          <volume>17</volume>
          <issue>9</issue>
          <fpage>1066</fpage>
          <lpage>1075</lpage>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3 Martins-Melo FR, Alencar CH, Ramos AN, Heukelbach J. Epidemiology of mortality related to Chagas' disease in Brazil, 1999-2007. PLoS Negl Trop Dis. 2012;6(2):e1508.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Martins-Melo</surname>
              <given-names>FR</given-names>
            </name>
            <name>
              <surname>Alencar</surname>
              <given-names>CH</given-names>
            </name>
            <name>
              <surname>Ramos</surname>
              <given-names>AN</given-names>
            </name>
            <name>
              <surname>Heukelbach</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Epidemiology of mortality related to Chagas' disease in Brazil, 1999-2007</article-title>
          <source>PLoS Negl Trop Dis</source>
          <year>2012</year>
          <volume>6</volume>
          <issue>2</issue>
          <elocation-id>e1508</elocation-id>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4 Costa R, Rassi A, Le&#227;o MIP. Estudo cl&#237;nico e epidemiol&#243;gico de pacientes submetidos a implante de marcapasso card&#237;aco artificial permanente: compara&#231;&#227;o dos portadores da doen&#231;a de Chagas com os de doen&#231;as degenerativas do sistema de condu&#231;&#227;o. Rev Bras Cir Cardiovasc. 2004;19(2):107-114.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Costa</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Rassi</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Le&#227;o</surname>
              <given-names>MIP</given-names>
            </name>
          </person-group>
          <article-title>Estudo cl&#237;nico e epidemiol&#243;gico de pacientes submetidos a implante de marcapasso card&#237;aco artificial permanente: compara&#231;&#227;o dos portadores da doen&#231;a de Chagas com os de doen&#231;as degenerativas do sistema de condu&#231;&#227;o</article-title>
          <source>Rev Bras Cir Cardiovasc</source>
          <year>2004</year>
          <volume>19</volume>
          <issue>2</issue>
          <fpage>107</fpage>
          <lpage>114</lpage>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5 Rassi A, Marin-Neto JA. Chagas disease. Lancet. 2010;375(9723):1388-402.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rassi</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Marin-Neto</surname>
              <given-names>JA</given-names>
            </name>
          </person-group>
          <article-title>Chagas disease</article-title>
          <source>Lancet</source>
          <year>2010</year>
          <volume>375</volume>
          <issue>9723</issue>
          <fpage>1388</fpage>
          <lpage>1402</lpage>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6 G&#252;rtler RE, Segura EL, Cohen JE. Congenital transmission of Trypanosoma cruzi infection in Argentina. Emerg Infect Dis. 2003;9(1):29-32.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>G&#252;rtler</surname>
              <given-names>RE</given-names>
            </name>
            <name>
              <surname>Segura</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Cohen</surname>
              <given-names>JE</given-names>
            </name>
          </person-group>
          <article-title>Congenital transmission of Trypanosoma cruzi infection in Argentina</article-title>
          <source>Emerg Infect Dis</source>
          <year>2003</year>
          <volume>9</volume>
          <issue>1</issue>
          <fpage>29</fpage>
          <lpage>32</lpage>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7 Howard EJ, Xiong X, Carlier Y, Sosa-Estani S, Buekens P. Frequency of the congenital transmission of Trypanosoma cruzi: a systematic review and meta-analysis. BJOG. 2014;121(1):22-33.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Howard</surname>
              <given-names>EJ</given-names>
            </name>
            <name>
              <surname>Xiong</surname>
              <given-names>X</given-names>
            </name>
            <name>
              <surname>Carlier</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Sosa-Estani</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Buekens</surname>
              <given-names>P</given-names>
            </name>
          </person-group>
          <article-title>Frequency of the congenital transmission of Trypanosoma cruzi: a systematic review and meta-analysis</article-title>
          <source>BJOG</source>
          <year>2014</year>
          <volume>121</volume>
          <issue>1</issue>
          <fpage>22</fpage>
          <lpage>33</lpage>
        </element-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <mixed-citation>8 Torrico F, Alonso-Vega C, Suarez E, Rodriguez P, Torrico MC, Dramaix M, et al. Maternal Trypanosoma cruzi infection, pregnancy outcome, morbidity, and mortality of congenitally infected and non-infected newborns in Bolivia. Am J Trop Med Hyg. 2004;70(2):201-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Torrico</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Alonso-Vega</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Suarez</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Rodriguez</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Torrico</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Dramaix</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Maternal Trypanosoma cruzi infection, pregnancy outcome, morbidity, and mortality of congenitally infected and non-infected newborns in Bolivia</article-title>
          <source>Am J Trop Med Hyg</source>
          <year>2004</year>
          <volume>70</volume>
          <issue>2</issue>
          <fpage>201</fpage>
          <lpage>209</lpage>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9 Ulmer H, Kollerits B, Kelleher C, Diem G, Concin H. Predictive accuracy of the SCORE risk function for cardiovascular disease in clinical practice: a prospective evaluation of 44 649 Austrian men and women. Eur J Cardiovasc Prev Rehabil. 2005;12(5):433-41.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ulmer</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Kollerits</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Kelleher</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Diem</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Concin</surname>
              <given-names>H</given-names>
            </name>
          </person-group>
          <article-title>Predictive accuracy of the SCORE risk function for cardiovascular disease in clinical practice: a prospective evaluation of 44 649 Austrian men and women</article-title>
          <source>Eur J Cardiovasc Prev Rehabil</source>
          <year>2005</year>
          <volume>12</volume>
          <issue>5</issue>
          <fpage>433</fpage>
          <lpage>441</lpage>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>10 Torrico F, Alonso-Vega C, Suarez E, Rodr&#237;guez P, Torrico MC, Dramaix M, et al. [Endemic level of congenital Trypanosoma cruzi infection in the areas of maternal residence and the development of congenital Chagas disease in Bolivia]. Rev Soc Bras Med Trop. 2005;38 (Suppl 2):17-20.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Torrico</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Alonso-Vega</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Suarez</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Rodr&#237;guez</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Torrico</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Dramaix</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Endemic level of congenital Trypanosoma cruzi infection in the areas of maternal residence and the development of congenital Chagas disease in Bolivia</article-title>
          <source>Rev Soc Bras Med Trop</source>
          <year>2005</year>
          <volume>38</volume>
          <supplement>Suppl 2</supplement>
          <fpage>17</fpage>
          <lpage>20</lpage>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>11 Salas NA, Cot M, Schneider D, Mendoza B, Santalla JA, Postigo J, et al. Risk factors and consequences of congenital Chagas disease in Yacuiba, south Bolivia. Trop Med Int Health. 2007;12(12):1498-505.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Salas</surname>
              <given-names>NA</given-names>
            </name>
            <name>
              <surname>Cot</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Schneider</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Mendoza</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Santalla</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Postigo</surname>
              <given-names>J</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Risk factors and consequences of congenital Chagas disease in Yacuiba, south Bolivia</article-title>
          <source>Trop Med Int Health</source>
          <year>2007</year>
          <volume>12</volume>
          <issue>12</issue>
          <fpage>1498</fpage>
          <lpage>1505</lpage>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12 Apt W, Zulantay I, Solari A, Ortiz S, Oddo D, Corral G, et al. Vertical transmission of Trypanosoma cruzi in the Province of Choapa, IV Region, Chile: Preliminary Report (2005-2008). Biol Res. 2010;43(3):269-74.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Apt</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Zulantay</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Solari</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Ortiz</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Oddo</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Corral</surname>
              <given-names>G</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Vertical transmission of Trypanosoma cruzi in the Province of Choapa, IV Region, Chile: Preliminary Report (2005-2008)</article-title>
          <source>Biol Res</source>
          <year>2010</year>
          <volume>43</volume>
          <issue>3</issue>
          <fpage>269</fpage>
          <lpage>274</lpage>
        </element-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <mixed-citation>13 Ostermayer AL, Passos AD, Silveira AC, Ferreira AW, Macedo V, Prata AR. [The national survey of seroprevalence for evaluation of the control of Chagas disease in Brazil (2001-2008)]. Rev Soc Bras Med Trop. 2011;44(Suppl 2):108-21.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ostermayer</surname>
              <given-names>AL</given-names>
            </name>
            <name>
              <surname>Passos</surname>
              <given-names>AD</given-names>
            </name>
            <name>
              <surname>Silveira</surname>
              <given-names>AC</given-names>
            </name>
            <name>
              <surname>Ferreira</surname>
              <given-names>AW</given-names>
            </name>
            <name>
              <surname>Macedo</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Prata</surname>
              <given-names>AR</given-names>
            </name>
          </person-group>
          <article-title>The national survey of seroprevalence for evaluation of the control of Chagas disease in Brazil (2001-2008)</article-title>
          <source>Rev Soc Bras Med Trop</source>
          <year>2011</year>
          <volume>44</volume>
          <supplement>Suppl 2</supplement>
          <fpage>108</fpage>
          <lpage>121</lpage>
        </element-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <mixed-citation>14 Bittencourt AL. Congenital Chagas disease. Am J Dis Child. 1976;130(1):97-103.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bittencourt</surname>
              <given-names>AL</given-names>
            </name>
          </person-group>
          <article-title>Congenital Chagas disease</article-title>
          <source>Am J Dis Child</source>
          <year>1976</year>
          <volume>130</volume>
          <issue>1</issue>
          <fpage>97</fpage>
          <lpage>103</lpage>
        </element-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <mixed-citation>15 Bittencourt AL. Possible risk factors for vertical transmission of Chagas' disease. Rev Inst Med Trop Sao Paulo. 1992;34(5):403-8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bittencourt</surname>
              <given-names>AL</given-names>
            </name>
          </person-group>
          <article-title>Possible risk factors for vertical transmission of Chagas' disease</article-title>
          <source>Rev Inst Med Trop Sao Paulo</source>
          <year>1992</year>
          <volume>34</volume>
          <issue>5</issue>
          <fpage>403</fpage>
          <lpage>408</lpage>
        </element-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <mixed-citation>16 Bern C, Verastegui M, Gilman RH, Lafuente C, Galdos-Cardenas G, Calderon M, et al. Congenital Trypanosoma cruzi transmission in Santa Cruz, Bolivia. Clin Infect Dis. 2009;49(11):1667-74.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bern</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Verastegui</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Gilman</surname>
              <given-names>RH</given-names>
            </name>
            <name>
              <surname>Lafuente</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Galdos-Cardenas</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Calderon</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Congenital Trypanosoma cruzi transmission in Santa Cruz, Bolivia</article-title>
          <source>Clin Infect Dis</source>
          <year>2009</year>
          <volume>49</volume>
          <issue>11</issue>
          <fpage>1667</fpage>
          <lpage>1674</lpage>
        </element-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <mixed-citation>17 Carlier Y, Torrico F, Sosa-Estani S, Russomando G, Luquetti A, Freilij H, et al. Congenital Chagas disease: recommendations for diagnosis, treatment and control of newborns, siblings and pregnant women. PLoS Negl Trop Dis. 2011;5(10):e1250.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Carlier</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Torrico</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Sosa-Estani</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Russomando</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Luquetti</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Freilij</surname>
              <given-names>H</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Congenital Chagas disease: recommendations for diagnosis, treatment and control of newborns, siblings and pregnant women</article-title>
          <source>PLoS Negl Trop Dis</source>
          <year>2011</year>
          <volume>5</volume>
          <issue>10</issue>
          <elocation-id>e1250</elocation-id>
        </element-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <mixed-citation>18 Nouvellet P, Cucunub&#225; ZM, Gourbi&#232;re S. Ecology, evolution and control of Chagas disease: a century of neglected modelling and a promising future. Adv Parasitol. 2015 Mar;87:135-91.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nouvellet</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Cucunub&#225;</surname>
              <given-names>ZM</given-names>
            </name>
            <name>
              <surname>Gourbi&#232;re</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
          <article-title>Ecology, evolution and control of Chagas disease: a century of neglected modelling and a promising future</article-title>
          <source>Adv Parasitol</source>
          <year>2015</year>
          <month>03</month>
          <volume>87</volume>
          <fpage>135</fpage>
          <lpage>191</lpage>
        </element-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <mixed-citation>19 Bonney KM. Chagas disease in the 21st century: a public health success or an emerging threat? Parasite. 2014;21:11.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bonney</surname>
              <given-names>KM</given-names>
            </name>
          </person-group>
          <article-title>Chagas disease in the 21st century: a public health success or an emerging threat?</article-title>
          <source>Parasite</source>
          <year>2014</year>
          <volume>21</volume>
          <fpage>11</fpage>
          <lpage>11</lpage>
        </element-citation>
      </ref>
      <ref id="B20">
        <label>20</label>
        <mixed-citation>20 Marin-Neto JA SM, Maciel BC. Cardiomyopathies and pericardial disease: Other cardiomyopathy. In: Yusuf S, Cairns J, Camm J, Fallen E, Gersh BJ, eds. Evidence Based Cardiology. 2nd ed. London: BMJ Publishing;2003.p.718-32.</mixed-citation>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Marin-Neto</surname>
              <given-names>JA SM</given-names>
            </name>
            <name>
              <surname>Maciel</surname>
              <given-names>BC</given-names>
            </name>
          </person-group>
          <chapter-title>Cardiomyopathies and pericardial disease: Other cardiomyopathy</chapter-title>
          <person-group person-group-type="editor">
            <name>
              <surname>Yusuf</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Cairns</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Camm</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Fallen</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Gersh</surname>
              <given-names>BJ</given-names>
            </name>
          </person-group>
          <source>Evidence Based Cardiology</source>
          <edition>2nd ed</edition>
          <publisher-loc>London</publisher-loc>
          <publisher-name>BMJ Publishing</publisher-name>
          <year>2003</year>
          <fpage>718</fpage>
          <lpage>732</lpage>
        </element-citation>
      </ref>
      <ref id="B21">
        <label>21</label>
        <mixed-citation>21 Dias JP, Bastos C, de Ara&#250;jo EG, Mascarenhas AV, Netto E, Grassi F, et al. [Outbreak of acute Chagas disease occurred in the state of Bahia, Brazil]. Rev Soc Bras Med Trop. 2006;39 (Suppl 3):135-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Dias</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Bastos</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>de Ara&#250;jo</surname>
              <given-names>EG</given-names>
            </name>
            <name>
              <surname>Mascarenhas</surname>
              <given-names>AV</given-names>
            </name>
            <name>
              <surname>Netto</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Grassi</surname>
              <given-names>F</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Outbreak of acute Chagas disease occurred in the state of Bahia, Brazil</article-title>
          <source>Rev Soc Bras Med Trop</source>
          <year>2006</year>
          <volume>39</volume>
          <supplement>Suppl 3</supplement>
          <fpage>135</fpage>
          <lpage>137</lpage>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
          <subj-group>
            <subject>Marca-passo</subject>
          </subj-group>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Implante de Marca-Passos em Crian&#231;as e Adolescentes Chag&#225;sicos no Brasil: Incid&#234;ncia Hist&#243;rica em 18 Anos</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Mizzaci</surname>
            <given-names>Carolina Christianini</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Souza</surname>
            <given-names>Thiago Gon&#231;alves Schroder e</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Targueta</surname>
            <given-names>Gabriel Pelegrineti</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>T&#243;tora</surname>
            <given-names>Ana Paula Frederico</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mateos</surname>
            <given-names>Juan Carlos Pach&#243;n</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mateos</surname>
            <given-names>Jos&#233; Carlos Pachon</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <aff id="aff2">
          <institution content-type="original">Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Thiago Gon&#231;alves Schroder e Souza,</bold> Av. Dr. Dante Pazzanese, 500. CEP 04012-909, Ibirapuera, S&#227;o Paulo, SP - Brasil. E-mail: <email>thiagojfx@gmail.com</email>, <email>thiago.schroder@usp.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Mizzaci CC, Souza TGS, Pach&#243;n-Mateos JC, Mateos JCP; Obten&#231;&#227;o de dados: Mizzaci CC, Targueta GP, T&#243;tora APF; An&#225;lise e interpreta&#231;&#227;o dos dados: Souza TGS, Targueta GP, T&#243;tora APF; An&#225;lise estat&#237;stica: Souza TGS; Reda&#231;&#227;o do manuscrito: Mizzaci CC, Souza TGS, Targueta GP, T&#243;tora APF, Pach&#243;n-Mateos JC; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Mizzaci CC, Pach&#243;n-Mateos JC, Mateos JCP.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>A doen&#231;a de Chagas mant&#233;m-se como s&#233;rio problema de sa&#250;de p&#250;blica e tem sido respons&#225;vel por aproximadamente 25% a 30% das indica&#231;&#245;es de estimula&#231;&#227;o card&#237;aca no Brasil.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Estudar as caracter&#237;sticas cl&#237;nicas e epidemiol&#243;gicas dos pacientes menores de 18 anos portadores de doen&#231;a de Chagas submetidos a implante de marca-passo no territ&#243;rio brasileiro entre 1994 e 2011, e sua tend&#234;ncia temporal.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Trata-se de um estudo retrospectivo que utilizou informa&#231;&#245;es coletadas pelo Registro Brasileiro de Marca-passo. As vari&#225;veis analisadas foram: ano do implante, localidade, idade, sexo, grupo &#233;tnico dos pacientes; classifica&#231;&#227;o funcional e os principais achados eletrocardiogr&#225;ficos de base.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Em um total de 183 123 implantes realizados entre 1994 e 2011, foram identificados 214 implantes de dispositivos de estimula&#231;&#227;o card&#237;aca em portadores de doen&#231;a de Chagas com idade inferior a 18 anos. A m&#233;dia de idade no momento do implante foi de 5,6 &#177; 6,2 anos. Bloqueios atrioventriculares de 2&#186; e 3&#186; graus foram respons&#225;veis por 71% das indica&#231;&#245;es. Dos procedimentos, 55,6% foram realizados na regi&#227;o sudeste. Em rela&#231;&#227;o ao total de implantes de marca-passo por ano, observamos um aumento importante e significante de implante por todas as causas. Entretanto, quando avaliamos a s&#233;rie temporal de implantes em pacientes com doen&#231;a de Chagas menores que 18 anos, observamos uma redu&#231;&#227;o expressiva e significativa no n&#250;mero anual de implantes.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>Observa-se uma redu&#231;&#227;o importante do n&#250;mero de implantes de marca-passo em crian&#231;as e adolescente chag&#225;sicos, o que sugere uma redu&#231;&#227;o da transmiss&#227;o vertical do parasita. </p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Estudos Retrospectivos</kwd>
        <kwd>Marca-Passo Artificial</kwd>
        <kwd>Crian&#231;a</kwd>
        <kwd>Adolescentes</kwd>
        <kwd>Doen&#231;a de Chagas</kwd>
        <kwd>Cardiomiopatia Chag&#225;sica</kwd>
        <kwd>Epidemiologia</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>End&#234;mica na Am&#233;rica do Sul e emergente na Europa e nos Estados Unidos, a doen&#231;a de Chagas mant&#233;m-se como s&#233;rio problema de sa&#250;de p&#250;blica. Somente no Brasil, estima-se que existam entre 2,9 e 7,2 milh&#245;es de pessoas com doen&#231;a de Chagas,<xref ref-type="bibr" rid="B1">1</xref> e que essa &#233; respons&#225;vel por cerca de seis mil mortes anualmente.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref> Conforme dados do Registro Brasileiro de Marca-passo (RBM), a doen&#231;a de Chagas historicamente tem sido respons&#225;vel por 25% a 30% de todas a indica&#231;&#245;es de estimula&#231;&#227;o card&#237;aca no pa&#237;s.<xref ref-type="bibr" rid="B4">4</xref>
				</p>
        <p>Al&#233;m do cont&#225;gio por meio das fezes infectadas dos triatom&#237;neos hemat&#243;fagos, o <italic>Trypanosoma cruzi</italic> pode ser transmitido por transfus&#227;o de sangue, transplante de &#243;rg&#227;os, consumo de alimentos ou bebidas contaminados e de m&#227;e para filho.<xref ref-type="bibr" rid="B5">5</xref> Com a melhora do controle do inseto vetor e da transmiss&#227;o por via transfusional, a transmiss&#227;o cong&#234;nita se tornou a mais importante forma de cont&#225;gio na maioria das &#225;reas end&#234;micas.<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B7">7</xref>
				</p>
        <p>A preval&#234;ncia da infec&#231;&#227;o pelo <italic>T. cruzi</italic> em gestantes pode variar entre 1% e 40%<xref ref-type="bibr" rid="B8">8</xref><sup>-</sup><xref ref-type="bibr" rid="B12">12</xref> e a taxa de transmiss&#227;o cong&#234;nita alcan&#231;a at&#233; 28,6%.<xref ref-type="bibr" rid="B7">7</xref> Estimativas recentes indicam que, anualmente, mais de quatorze mil rec&#233;m-nascidos apresentam doen&#231;a de Chagas cong&#234;nita na Am&#233;rica Latina. Em uma pesquisa realizada em &#225;reas rurais do Brasil entre 2001 e 2008, incluindo 105 mil crian&#231;as de zero a cinco anos, foi observado uma preval&#234;ncia de infec&#231;&#227;o pelo <italic>T. cruzi</italic> de 0,03%, sendo 0,02% por prov&#225;vel transmiss&#227;o cong&#234;nita e apenas 0,01% atribu&#237;dos &#224; transmiss&#227;o vetorial.<xref ref-type="bibr" rid="B13">13</xref>
				</p>
        <p>A maioria dos casos de infec&#231;&#227;o cong&#234;nita pelo <italic>T. cruzi</italic> s&#227;o assintom&#225;ticos, entretanto ela pode resultar em parto prematuro, baixo peso ao nascer, natimortos e manifesta&#231;&#245;es cl&#237;nicas da doen&#231;a de Chagas ao nascimento.<xref ref-type="bibr" rid="B14">14</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref> Como a transmiss&#227;o cong&#234;nita n&#227;o pode ser evitada, o diagn&#243;stico precoce e o tratamento dos casos cong&#234;nitos s&#227;o prioridades nos programas de controle da doen&#231;a de Chagas.<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref>
				</p>
        <p>Diante das altera&#231;&#245;es demogr&#225;ficas e mudan&#231;as nas principais formas de transmiss&#227;o, com destaque ao aumento da import&#226;ncia da transmiss&#227;o vertical, ainda s&#227;o escassas as informa&#231;&#245;es sobre como essas altera&#231;&#245;es poderiam influenciar na evolu&#231;&#227;o ou tratamento dos pacientes. Desta forma, com intuito de aumentar as informa&#231;&#245;es que permeiam o tema, objetivamos estudar as caracter&#237;sticas cl&#237;nicas e epidemiol&#243;gicas dos pacientes menores de 18 anos portadores de doen&#231;a de Chagas submetidos &#224; implante de marca-passo card&#237;aco permanente no territ&#243;rio brasileiro entre 1994 e 2011.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todo</title>
        <p>Trata-se de um estudo que utilizou informa&#231;&#245;es do sistema de banco de dados do RBM, oficializado pelo Minist&#233;rio da Sa&#250;de (portaria MS/SAS n&#186; 41, 17 de dezembro de 1994), e organizado pelo Departamento de Estimula&#231;&#227;o Card&#237;aca Artificial da Sociedade Brasileira de Cirurgia Cardiovascular (DECA-SBCCV). Trata-se de uma base de dados que tem como objetivo o cadastramento dos procedimentos relacionados &#224; estimula&#231;&#227;o card&#237;aca artificial permanente no territ&#243;rio brasileiro. Para tanto, exige o preenchimento de formul&#225;rio pr&#243;prio padronizado em todos os implantes de geradores realizados no Brasil. Os formul&#225;rios preenchidos s&#227;o encaminhados para um centro regulador onde as informa&#231;&#245;es s&#227;o cadastradas no sistema.</p>
        <p>As vari&#225;veis analisadas foram: ano em que o implante foi realizado, a localidade de origem, a idade, o sexo e o grupo &#233;tnico dos pacientes, classifica&#231;&#227;o funcional para insufici&#234;ncia card&#237;aca, utilizando os crit&#233;rios da NYHA (<italic>New York Heart Association</italic>) e o principal achado eletrocardiogr&#225;fico que justificou a indica&#231;&#227;o do marca-passo.</p>
        <p>As vari&#225;veis categ&#243;ricas foram representadas por frequ&#234;ncias absolutas e relativas, e as vari&#225;veis cont&#237;nuas por m&#233;dia e desvio padr&#227;o. Para an&#225;lise estat&#237;stica utilizou-se o programa SPSS (<italic>Statistical Package for the Social Sciences</italic>).</p>
        <p>Para avalia&#231;&#227;o da varia&#231;&#227;o temporal do n&#250;mero de implantes de marca-passo nas s&#233;ries estudadas, foi empregado o teste de Jonckheere-Terpstra para tend&#234;ncia. O erro alfa admitido, que preenche o crit&#233;rio de signific&#226;ncia, foi de 5%. </p>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>Entre 1994 e 2011, foram identificados 183 123 pacientes submetidos a primeiro implante de marca-passo no Brasil. Desse total, 35 204 foram realizados em indiv&#237;duos com diagn&#243;stico de doen&#231;a de Chagas, sendo 214 procedimentos cir&#250;rgicos referentes a implantes de dispositivos de estimula&#231;&#227;o card&#237;aca em pacientes com idade menor ou igual a 17 anos.</p>
        <p>No grupo dos pacientes com doen&#231;a de Chagas menores de 18 anos submetidos a implante de marca-passo, a m&#233;dia de idade foi de 5,62 &#177; 6,2 anos &#224; &#233;poca dos implantes. Desses pacientes, 44,8% eram do sexo feminino, com m&#233;dia de idade de 5,2 &#177; 5,8 anos, e 55,2% eram do sexo masculino com m&#233;dia de idade de 6,1 (&#177; 6,5) anos. A <xref ref-type="fig" rid="f4">Figura 1</xref> mostra a frequ&#234;ncia absoluta anual dos implantes realizados nesse grupo no decorrer dos 18 anos avaliados, com uma redu&#231;&#227;o importante no n&#250;mero de implantes. A m&#233;dia de implantes no primeiro tri&#234;nio avaliado (1994 a 1996) foi de 20,6 implantes/ano, e a m&#233;dia do &#250;ltimo tri&#234;nio (2009 a 2011) foi de 4,3 implantes/anos, indicando uma redu&#231;&#227;o de 79,1% entre os referidos per&#237;odos.</p>
        <p>
          <fig id="f4">
            <label>Figura 1</label>
            <caption>
              <title>Distribui&#231;&#227;o anual dos implantes de marca-passo em pacientes menores de 18 anos portadores de doen&#231;a de Chagas.</title>
            </caption>
            <attrib>Fonte: Registro Brasileiro de Marca-passos.</attrib>
            <graphic xlink:href="1678-4170-abc-108-06-0546-70074-gf01-pt.jpg"/></fig>
        </p>
        <p>A distribui&#231;&#227;o dos procedimentos de acordo com a origem geogr&#225;fica dos pacientes mostrou grande diversidade regional. A maioria dos pacientes submetidos a implantes &#233; oriunda da regi&#227;o Sudeste (55,6% dos casos), seguida pela regi&#227;o centro-oeste (25,7% dos casos).</p>
        <p>O grupo &#233;tnico branco representou a maioria dos pacientes, 49,5% dos implantes, seguido dos mesti&#231;os e negros, 20,1% e 14%, respectivamente. Em rela&#231;&#227;o &#224; sintomatologia, os pacientes apresentaram predom&#237;nio de insufici&#234;ncia card&#237;aca nas classes funcionais (CF) III e IV de NYHA. No total, 100 (46,7%) pacientes apresentavam sintomas aos m&#233;dios ou pequenos esfor&#231;os e 68 (31,8%) pacientes tinham sintomas ao repouso (<xref ref-type="table" rid="t2">Tabela 1</xref>).</p>
        <table-wrap id="t2">
          <label>Tabela 1</label>
          <caption>
            <title>Caracter&#237;sticas basais dos pacientes menores de 18 anos com doen&#231;a de Chagas submetidos a implante de dispositivo de estimula&#231;&#227;o card&#237;aca artificial entre 1994 e 2011</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="33%"/>
              <col width="33%"/>
              <col width="33%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Pacientes (n)</th>
                <th align="center">
								</th>
                <th align="center">214</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Idade (anos)</td>
                <td align="center">
								</td>
                <td align="center">5,62 &#177; 6,2</td>
              </tr>
              <tr>
                <td align="left" rowspan="2" valign="top">Sexo</td>
                <td align="center">Masculino</td>
                <td align="center">118 (55,2%)</td>
              </tr>
              <tr>
                <td align="center">Feminino</td>
                <td align="center">96 (44,8%)</td>
              </tr>
              <tr>
                <td align="left" rowspan="9" valign="top">Estado (UF) de origem</td>
                <td align="center">S&#227;o Paulo</td>
                <td align="center">59 (27,6%)</td>
              </tr>
              <tr>
                <td align="center">Minas Gerais</td>
                <td align="center">59 (27,6%)</td>
              </tr>
              <tr>
                <td align="center">Goi&#225;s</td>
                <td align="center">36 (16,8%)</td>
              </tr>
              <tr>
                <td align="center">Distrito Federal</td>
                <td align="center">19 (8,9%)</td>
              </tr>
              <tr>
                <td align="center">Paran&#225;</td>
                <td align="center">13 (6,1%)</td>
              </tr>
              <tr>
                <td align="center">Bahia</td>
                <td align="center">8 (3,7%)</td>
              </tr>
              <tr>
                <td align="center">Alagoas</td>
                <td align="center">5 (2,3%)</td>
              </tr>
              <tr>
                <td align="center">Pernambuco</td>
                <td align="center">5 (2,3%)</td>
              </tr>
              <tr>
                <td align="center">Outros</td>
                <td align="center">10 (4,7%)</td>
              </tr>
              <tr>
                <td align="left" rowspan="4" valign="top">Etnia</td>
                <td align="center">Branca</td>
                <td align="center">106 (49,5%)</td>
              </tr>
              <tr>
                <td align="center">Mesti&#231;o</td>
                <td align="center">43 (20,1%)</td>
              </tr>
              <tr>
                <td align="center">Negro</td>
                <td align="center">30 (14,0%)</td>
              </tr>
              <tr>
                <td align="center">N&#227;o declarados</td>
                <td align="center">35 (16,3%)</td>
              </tr>
              <tr>
                <td align="left" rowspan="5" valign="top">Sintomas</td>
                <td align="center">Assintom&#225;ticos</td>
                <td align="center">19 (8,9%)</td>
              </tr>
              <tr>
                <td align="center">Sintomas aos grandes esfor&#231;os</td>
                <td align="center">22 (10,3%)</td>
              </tr>
              <tr>
                <td align="center">Sintomas aos m&#233;dios ou pequenos esfor&#231;os</td>
                <td align="center">100 (46,7%)</td>
              </tr>
              <tr>
                <td align="center">Sintomas em repouso</td>
                <td align="center">68 (31,8%)</td>
              </tr>
              <tr>
                <td align="center">N&#227;o informado</td>
                <td align="center">5 (2,3%)</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>O principal achado eletrocardiogr&#225;fico que indicou o implante do sistema de estimula&#231;&#227;o foi bloqueio atrioventricular (BAV) de 2&#176; e 3&#176; grau, totalizando 71% dos casos. A maioria desses eram BAV totais com QRS largo, com 42% de incid&#234;ncia, enquanto os BAV totais com QRS estreito foram informados em 10% dos pacientes (<xref ref-type="fig" rid="f5">Figura 2</xref>).</p>
        <p>
          <fig id="f5">
            <label>Figura 2</label>
            <caption>
              <title>Achados eletrocardiogr&#225;fcos que justifcaram o implante inicial de marca-passo em pacientes portadores de Doen&#231;a de Chagas com idade inferior a 18 anos. BAV: bloqueio atrioventricular; BRE: bloqueio do ramo esquerdo.</title>
            </caption>
            <attrib>Fonte: Registro Brasileiro de Marca-passos.</attrib>
            <graphic xlink:href="1678-4170-abc-108-06-0546-70074-gf02-pt.jpg"/></fig>
        </p>
        <p>Em rela&#231;&#227;o ao total de implantes de marca-passo por ano (<xref ref-type="fig" rid="f6">Figura 3</xref>), observamos um aumento importante e estatisticamente significante no total de implante por todas as causas. Quando avaliamos a s&#233;rie temporal do n&#250;mero de implantes em pacientes com doen&#231;a de Chagas de todas as idades, sua discreta varia&#231;&#227;o n&#227;o apresenta signific&#226;ncia estat&#237;stica, podendo ser origin&#225;ria de acaso (P para tend&#234;ncia = 0,5). Entretanto, a s&#233;rie temporal que avalia implantes em pacientes com doen&#231;a de Chagas e menores que 18 anos (<xref ref-type="fig" rid="f4">Figuras 1</xref> e <xref ref-type="fig" rid="f6">3</xref>), observamos uma redu&#231;&#227;o significativa do n&#250;mero de implantes ao longo dos tri&#234;nios (P para tend&#234;ncia &lt; 0,001).</p>
        <p>
          <fig id="f6">
            <label>Figura 3</label>
            <caption>
              <title>Gr&#225;fco comparativo entre o total anual de implantes de marca-passos no Brasil por todas as causas (losango), o total de implantes em pacientes portadores de Doen&#231;a de Chagas (quadrado), e o total de implantes em portadores de doen&#231;a de Chagas menores que 18 anos (tri&#226;ngulo). Valores de P para tend&#234;ncia de varia&#231;&#227;o de cada s&#233;rie ao logo dos tri&#234;nios.</title>
            </caption>
            <attrib>Fonte: Registro Brasileiro de Marca-passos.</attrib>
            <graphic xlink:href="1678-4170-abc-108-06-0546-70074-gf03-pt.jpg"/></fig>
        </p>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Em 1999, a OPAS (Organiza&#231;&#227;o Pan-Americana de Sa&#250;de) declarou que o inseto vetor da Doen&#231;a de Chagas (<italic>Triatoma infestans</italic>) havia sido totalmente eliminado do ambiente domiciliar no Brasil, Chile e Uruguai e em grande parte da Argentina, Bol&#237;via e Paraguai.<xref ref-type="bibr" rid="B18">18</xref> No entanto, apesar dos recentes avan&#231;os no controle da transmiss&#227;o do <italic>T. Cruzi</italic>, a Doen&#231;a de Chagas permanece como um importante problema de sa&#250;de p&#250;blica na Am&#233;rica Latina, com um impacto anual de 430.000 DALYs (anos de vida ajustados para incapacidade <italic>- Disability-Adjusted Life Years</italic>).<xref ref-type="bibr" rid="B19">19</xref>Depreende-se desse fato duas hip&#243;teses principais:</p>
        <p>
          <list list-type="order">
            <list-item>
              <p>h&#225; um gasto continuado ou mesmo crescente no cuidado a portadores de doen&#231;a de Chagas cr&#244;nica, com destaque &#224; Cardiomiopatia Chag&#225;sica Cr&#244;nica (CCC);</p>
            </list-item>
            <list-item>
              <p>n&#227;o existe controle efetivo de todas as formas de transmiss&#227;o do parasita, gerando preocupa&#231;&#227;o em rela&#231;&#227;o &#224; transmiss&#227;o por transfus&#227;o sangu&#237;nea e, principalmente, &#224; transmiss&#227;o vertical do <italic>T.cruzi.</italic></p>
            </list-item>
          </list>
        </p>
        <p>Dados do Registro Brasileiro de Marca-passos geram informa&#231;&#245;es &#250;teis &#224; medida que refletem a morbidade da CCC. Entre os indiv&#237;duos infectados, aproximadamente 20% desenvolvem a CCC, com alto risco de BAV e morte s&#250;bita card&#237;aca.<xref ref-type="bibr" rid="B20">20</xref> Descrevemos, em nosso estudo, o interessante fato de que, apesar de haver um aumento no total de implantes de marca-passo no territ&#243;rio brasileiro, o n&#250;mero de procedimentos anuais em pacientes chag&#225;sicos permanece est&#225;vel. Tal fato reflete uma diminui&#231;&#227;o relativa da contribui&#231;&#227;o da CCC e aumento da contribui&#231;&#227;o de outras etiologias - como degenera&#231;&#227;o senil do sistema de condu&#231;&#227;o - nas indica&#231;&#245;es de estimula&#231;&#227;o card&#237;aca artificial. Esse achado pode se dever ao melhor controle da transmiss&#227;o vetorial e transfusional da Doen&#231;a de Chagas, bem como ao aumento da expectativa de vida da popula&#231;&#227;o brasileira.<xref ref-type="bibr" rid="B21">21</xref>
				</p>
        <p>O achado de maior relev&#226;ncia em nosso estudo foi a queda significativa na indica&#231;&#227;o de estimula&#231;&#227;o card&#237;aca artificial em indiv&#237;duos com menos de 18 anos, e pode refletir melhor controle de todas as formas de transmiss&#227;o da Doen&#231;a de Chagas no Brasil nas duas &#250;ltimas d&#233;cadas. Como j&#225; comentado, o combate ao inseto vetor foi parte fundamental nesse resultado, mas tamb&#233;m h&#225; que se destacar os avan&#231;os no controle da transmiss&#227;o do <italic>T.cruzi</italic> por transfus&#227;o sangu&#237;nea e a manuten&#231;&#227;o de baixos n&#237;veis de transmiss&#227;o vertical em nosso territ&#243;rio considerando que as doen&#231;as do sistema de condu&#231;&#227;o card&#237;aco na CCC constituem um evento final na hist&#243;ria natural dessa enfermidade, requerendo anos para sua instala&#231;&#227;o. No final da d&#233;cada de 80, instituiu-se no Brasil a obrigatoriedade da triagem de infec&#231;&#227;o por <italic>T.cruzi</italic> nos doadores de sangue. Previamente a essa medida, acreditava-se que 20 000 casos novos por ano de doen&#231;a de Chagas eram atribu&#237;veis &#224; transmiss&#227;o transfusional, e hoje o risco estimado de contamina&#231;&#227;o de hemoderivados pelo <italic>T.cruzi</italic> pode ser menor que 1 por 1.000.000 de transfus&#245;es.<xref ref-type="bibr" rid="B21">21</xref>
				</p>
        <p>A transmiss&#227;o vertical da Doen&#231;a de Chagas ganhou destaque ap&#243;s a melhoria do controle das outras formas de transmiss&#227;o no Brasil; entretanto n&#227;o existem dados conclusivos sobre sua import&#226;ncia absoluta no nosso pa&#237;s. A preval&#234;ncia da infec&#231;&#227;o em gestantes oscila entre 0,1 a 8,5%, e a taxa de transmiss&#227;o vertical varia de 0 a 5,2%, segundo uma recente revis&#227;o sistem&#225;tica.<xref ref-type="bibr" rid="B1">1</xref> A redu&#231;&#227;o da transmiss&#227;o vertical tamb&#233;m &#233; corroborada pelo fato de que doen&#231;as do sistema de condu&#231;&#227;o card&#237;aco na CCC constituem um evento final na hist&#243;ria natural dessa enfermidade, requerendo anos para sua instala&#231;&#227;o.</p>
        <p>Outro dado relevante do nosso estudo &#233; a distribui&#231;&#227;o desigual do n&#250;mero de implantes de marca-passo no territ&#243;rio nacional, nem sempre respeitando as regi&#245;es de maior preval&#234;ncia da CCC. Al&#233;m da concentra&#231;&#227;o dos principais servi&#231;os p&#250;blicos de assist&#234;ncia &#224; sa&#250;de nas grandes cidades, deve-se considerar, ainda, a possibilidade de pouco treinamento de especialistas em estimula&#231;&#227;o card&#237;aca artificial para implante em crian&#231;as, o que leva &#224; concentra&#231;&#227;o desses procedimentos em centros terci&#225;rios de capitais como S&#227;o Paulo.</p>
        <p>O presente estudo apresenta limita&#231;&#245;es inerentes ao seu desenho. Primeiro o estudo, baseia-se em uma base de dados sujeita &#224; heterogeneidade entre os respons&#225;veis por seu preenchimento, tornando a informa&#231;&#227;o menos precisa. Segundo, o estudo apenas nos permite tra&#231;ar hip&#243;teses de causalidade em rela&#231;&#227;o &#224;s tend&#234;ncias nos cuidados &#224; doen&#231;a de Chagas nos &#250;ltimos anos, tanto por se tratar de uma an&#225;lise retrospectiva, quanto por utilizar uma vari&#225;vel que n&#227;o reflete perfeitamente o todo. Apesar dessas limita&#231;&#245;es, consideramos que o estudo prov&#234; informa&#231;&#245;es de grande utilidade para o planejamento dos sistemas de sa&#250;de.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>Observa-se uma redu&#231;&#227;o importante do n&#250;mero de implantes de marca-passo em crian&#231;as e adolescente chag&#225;sicos no territ&#243;rio brasileiro, o que sugere um melhor controle de todas as formas de transmiss&#227;o da doen&#231;a de Chagas no Brasil nas duas &#250;ltimas d&#233;cadas e redu&#231;&#227;o da transmiss&#227;o vertical do parasita.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p><bold>Fontes de financiamento</bold> O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p><bold>Vincula&#231;&#227;o acad&#234;mica</bold> N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
