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  <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">vG849tcJXTJcXPP6LqgZj6P</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2019000900345</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2019005001305</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20190141</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Rheumatic Fever: A Disease without Color</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-8293-8611</contrib-id>
          <name>
            <surname>Figueiredo</surname>
            <given-names>Estev&#227;o Tavares de</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-0502-4090</contrib-id>
          <name>
            <surname>Azevedo</surname>
            <given-names>Luciana</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1106-4176</contrib-id>
          <name>
            <surname>Rezende</surname>
            <given-names>Marcelo Lacerda</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2523-6111</contrib-id>
          <name>
            <surname>Alves</surname>
            <given-names>Cristina Garcia</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina de Ribeir&#227;o Preto</institution>
        <addr-line>
          <city>Ribeir&#227;o Preto</city>
          <state>SP</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Faculdade de Medicina de Ribeir&#227;o Preto (FMRP) da Universidade de S&#227;o Paulo (USP), Ribeir&#227;o Preto, SP - Brazil</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Universidade Federal de Alfenas</institution>
        <addr-line>
          <city>Alfenas</city>
          <state>MG</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Federal de Alfenas, Alfenas, MG - Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Estev&#227;o Tavares de Figueiredo</bold> Departamento de Cl&#237;nica M&#233;dica da FMRP - USP - Avenida Bandeirantes, 3900. postal Code 14049-900, Ribeir&#227;o Preto, SP - Brazil E-mail: <email>etavaresdefigueiredo@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research, Statistical analysis and Critical revision of the manuscript for intellectual content: Figueiredo ET, Azevedo L, Rezende ML; Acquisition of data: Figueiredo ET, Alves CG; Analysis and interpretation of the data: Figueiredo ET, Azevedo L, Rezende ML, Alves CG; Writing of the manuscript: Figueiredo ET, Azevedo L, Rezende ML, Alves CG.</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 date-type="pub" publication-format="electronic">
        <day>29</day>
        <month>07</month>
        <year>2019</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>09</month>
        <year>2019</year>
      </pub-date>
      <volume>113</volume>
      <issue>3</issue>
      <fpage>345</fpage>
      <lpage>354</lpage>
      <history>
        <date date-type="received">
          <day>17</day>
          <month>08</month>
          <year>2018</year>
        </date>
        <date date-type="rev-recd">
          <day>15</day>
          <month>11</month>
          <year>2018</year>
        </date>
        <date date-type="accepted">
          <day>19</day>
          <month>12</month>
          <year>2018</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://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</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Brazil has approximately 30.000 cases of Acute Rheumatic Fever (ARF) annually. A third of cardiovascular surgeries performed in the country are due to the sequelae of rheumatic heart disease (RHD), which is an important public health problem.</p>
        </sec>
        <sec>
          <title>Objectives:</title>
          <p>to analyze the historical series of mortality rates and disease costs, projecting future trends to offer new data that may justify the need to implement a public health program for RF.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p> we performed a cross-sectional study with a time series analysis based on data from the Hospital Information System of Brazil from 1998 to 2016. Simple linear regression models and Holt&#8217;s Exponential Smoothing Method were used to model the behavior of the series and to do forecasts. The results of the tests with a value of p &lt; 0.05 were considered statistically significant.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>each year, the number of deaths due to RHD increased by an average of 16.94 units and the mortality rate from ARF increased by 215%. There was a 264% increase in hospitalization expenses for RHD and RHD mortality rates increased 42.5% (p-value &lt; 0.05). The estimated mortality rates for ARF and RHD were, respectively, 2.68 and 8.53 for 2019. The estimated cost for RHD in 2019 was US$ 26.715.897,70.</p>
        </sec>
        <sec>
          <title>Conclusions:</title>
          <p>according to the Brazilian reality, the 1-year RHD expenses would be sufficient for secondary prophylaxis (considering a Benzatin Penicillin G dose every 3 weeks) in 22.574 people for 10 years. This study corroborates the need for public health policies aimed at RHD.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Rheumatic Fever</kwd>
        <kwd>Rheumatic Heart Disease</kwd>
        <kwd>Cardiovascular Surgical Procedures/mortality</kwd>
        <kwd>Hospitalization/economics</kwd>
        <kwd>Antibiotic Prophylaxys/economics</kwd>
        <kwd>Public Health Policy</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>According to the Brazilian Institute of Geography and Statistics (IBGE), Brazil has 10 million cases of pharyngotonsillitis every year, leading to approximately 30.000 cases of Acute Rheumatic Fever (ARF).<xref ref-type="bibr" rid="B1">1</xref> Rheumatic Heart Disease (RHD) has a low incidence in developed countries, with 0.1 to 0.4 cases/1,000 school children in the US, while in Brazil these values are 7 cases/1.000 school children, showing that it is directly associated with environmental and socioeconomic factors.<xref ref-type="bibr" rid="B2">2</xref> Approximately 70% of the patients with acute RF develop carditis and a third of the cardiovascular surgeries performed in Brazil are due to of RHD sequelae.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref> RF was responsible for 5.1 million potential disability-adjusted life years (DALYs), resulting from 280.000 deaths in 2004, and it was the seventh and eighth causes of mortality and morbidity due to neglected diseases, respectively.<xref ref-type="bibr" rid="B5">5</xref>
			</p>
      <p>Rheumatic fever is a disease with a cross-linked autoimmune nature triggered by susceptible host response after pharyngotonsillitis by Group A &#946;-hemolytic <italic>Streptococcus.</italic><xref ref-type="bibr" rid="B6">6</xref><sup>-</sup><xref ref-type="bibr" rid="B8">8</xref> The implementation of treatment for pharyngotonsillitis by Group A &#946;-hemolytic <italic>Streptococcus</italic> with Benzathine Penicillin G (BPG) within nine days of symptom onset can eradicate the infection and prevent a first outbreak of acute RF<xref ref-type="bibr" rid="B3">3</xref> or a new outbreak,<xref ref-type="bibr" rid="B9">9</xref> which was already advocated by the WHO in 1955.<xref ref-type="bibr" rid="B10">10</xref> Unfortunately, the expected infection eradication rates do not seem to have been reached in Brazil, as shown by our analyses of data from the Health Information System (SIH) from the Brazilian National Health System (SUS).<xref ref-type="bibr" rid="B11">11</xref>
			</p>
      <p>SUS guarantees universal and egalitarian access to health care and services to everyone in the national territory. Therefore, Brazil&#8217;s health policies include care by the public (SUS) and the private sectors (supplementary healthcare, or private health plans), plus care by the private sector within the public sector (complementary health) and by the public sector within the private sector (regulation, inspection, surveillance). Herein, we disclose the cost analysis of health care and services related to RF and RHD incurred by SUS, i.e. under public management, which is different from that of the private systems.</p>
      <p>Considering the presented data and the absence of a national RF and RHD prevention program, the objective of this study was to analyze the historical series of mortality rates and disease costs, projecting future trends to offer new data that may justify the need to implement a public health program for RF. In addition, we estimate the annual costs of the diseases and their comorbidities in Brazil. Moreover, the RHD mortality rate was compared with breast (BC) and prostate (PC) cancer mortality rates, which already have implemented public health programs, such as the case of the Pink October<xref ref-type="bibr" rid="B12">12</xref> and the Blue November,<xref ref-type="bibr" rid="B13">13</xref> respectively.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>A cross-sectional ecological study with a time series analysis was developed to analyze the historical series of mortality rates and disease, using data from the SIH/SUS<xref ref-type="bibr" rid="B11">11</xref> from 1998 to 2016. The year 2017 was not included in this study because the data were still subject to updates.</p>
      <p>To estimate the annual cost of the diseases and their comorbidities in Brazil, first we determined the costs associated to the diagnosis of ARF, primary and secondary prophylaxis of RHD, as well as public expenses associated to the consequences of RHD, such as interventional procedures and hospitalizations for heart failure, atrial fibrillation, ischemic stroke and infective endocarditis. For this purpose, the data were obtained as follows: the procedures required for the diagnosis of ARF and Jones Criteria, which have been reviewed at irregular intervals by the American Heart Association (AHA), adjusted for RHD. For hospitalization costs, we considered the mean length of hospital stay of 7 days for ischemic stroke, heart failure 4 days, 4 days for atrial fibrillation and 17 days for infective endocarditis.<xref ref-type="bibr" rid="B14">14</xref> The data related to cost of the procedures required for the diagnosis of ARF/RHD and hospitalizations due to consequences of RHD were taken from the database of the Table Management System of Procedures, Medical drugs, Orthotics, Prosthetics and Special Materials of SUS (SIGTAP)<xref ref-type="bibr" rid="B14">14</xref> and the Drug Market Regulation Chamber (CMED) of the National Agency of Sanitary Surveillance (ANVISA).<xref ref-type="bibr" rid="B15">15</xref> These data are available at the Hospital Information Systems - SIH/SUS -Brazilian Health System. Second, we developed a hypothetical scenario based on the current panorama of rheumatic fever in Brazil, crossing data from the Brazilian Institute of Geography and Statistics with data from the REMEDY study<xref ref-type="bibr" rid="B16">16</xref> with their respective morbidities in numbers, to estimate the number of cases. The REMEDY study involved 25 sites in 12 African countries, Yemen and India. Countries were grouped into three income categories: low-income countries (Ethiopia, Kenya, Malawi, Rwanda, Uganda and Zambia), low-middle income countries (Egypt, India, Mozambique, Nigeria, Sudan and Yemen) and middle-income countries (Namibia and South Africa).<xref ref-type="bibr" rid="B16">16</xref> The costs obtained were multiplied by the number of cases of group A Streptococcus (GAS) infection, ARF, RHD, and RHD morbidity.</p>
      <p>Moreover, the RHD mortality rate was compared with breast (BC) and prostate (PC) cancer mortality rates, which was performed taking in account the period of 18 years (1998 to 2016), using data from the Mortality Information System's (SIM) of SUS - DATASUS,<xref ref-type="bibr" rid="B11">11</xref> responsible for the maintenance of mortality data in Brazil. For this comparison, a simple linear regression was adjusted to each case (RHD, PC, and BC).</p>
      <p>The present study used only secondary data obtained from public access sources. The approval of this study was waived by the Research Ethics Committee, as established in Resolution 510 of the National Health Council (CNS) of April 7, 2016.</p>
      <sec>
        <title>Statistical analyses</title>
        <p>To evaluate the trend of the historical series, simple linear regression models were adjusted. When working with time series, it is common to find problems of heteroscedasticity and autocorrelation. In order to deal with these problems and to allow the performance of valid inferences for the adjusted models, as well as to guarantee the robustness of the models, the HAC (Heteroskedasticity and Autocorrelation Consistent) was used for the covariance matrix of the estimated coefficients.<xref ref-type="bibr" rid="B17">17</xref> To model the behavior of the series and make predictions, Holt's Exponential Smoothing Method was used.<xref ref-type="bibr" rid="B18">18</xref> R software (version 3.2.4) was used for the statistical analysis. The results of the tests with a value of p &lt; 0.05 were considered statistically significant. The limitation of this study was the analysis of the SIH (SUS) database,<xref ref-type="bibr" rid="B11">11</xref> of which data are entered every two months or more, limiting confidence only to total annual data.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>Mortality rates from Acute Rheumatic Fever (ARF) and Rheumatic Heart Disease (RHD) showed an increasing pattern throughout the analysis period (<xref ref-type="fig" rid="f1">Figure 1</xref>). The ARF mortality rate increased from 0.80 in 1998 to 2.52 in 2016, a growth of 215%, with an increase of 0.12 units, on average, with each passing year (<xref ref-type="fig" rid="f1">Figure 1A</xref>). The RHD mortality rate was 5.77 in 1998, increasing to 8.22 in 2016 (a growth of 42.5%), showing an average rate increase of 0.15 units per year (<xref ref-type="fig" rid="f1">Figure 1</xref>C). Using Holt&#8217;s Exponential Smoothing, it was possible to perform mortality estimates for ARF and RHD. The predicted values for ARF mortality rate for 2018 and 2019 were, respectively, 2.59 and 2.68, while the predicted values for RHD mortality rates were 8.43 for 2018 and 8.53 for 2019.</p>
      <p>
        <fig id="f1">
          <label>Figure 1</label>
          <caption>
            <title>Growth trends and predicted values for Acute Rheumatic Fever (ARF) and Rheumatic Heart Disease (RHD) mortality rates. The model equation for the trend of the ARF (A) mortality rate was ARF<sub>MT</sub> = &#8211;237,79 + 0,12* Year, whereas for the trend of the RHD mortality rate (C) it was RDH<sub>MT</sub> = &#8211;286,11 + 0,15* Year. It should be noted that all trends were significant (p-value &lt; 0.050), evidencing the increasing trend of the series over time.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-113-03-0345-90141-gf01.jpg"/></fig>
      </p>
      <p>Although these numbers may be underestimated de to the lack of a health surveillance strategy, which will be discussed later, 732 deaths were recorded in 2003 and after a linear regression (p-value &lt; 0.005) of the entire studied period, it is observed that the number of deaths increases on average 16,94 units each year.</p>
      <p>Regarding the cost analyses, <xref ref-type="table" rid="t1">Table 1</xref> shows a detailed description of the obtained costs for ARF diagnosis, the most common interventional procedures in RHD, and the costs of hospitalization due to the consequences of RHD, for a hypothetical patient in the context of the Brazilian public health system.</p>
      <table-wrap id="t1">
        <label>Table 1</label>
        <caption>
          <title>A detailed description of the costs associated with the diagnosis of Acute Rheumatic Fever, as well as the costs of interventional procedures and hospitalizations due to Rheumatic Heart Disease in the context of the public health system of Brazil (values set for 2016)</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
            <col width="254%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left" rowspan="2">Diagnosis and treatment</th>
              <th align="center" rowspan="2">Procedures</th>
              <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">Individual cost per procedure</th>
            </tr>
            <tr>
              <th align="center">(R$)</th>
              <th align="center">(US$)<sup><xref ref-type="table-fn" rid="TFN3">&#8224;</xref></sup></th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left" rowspan="8">Procedures needed for the diagnosis of ARF<xref ref-type="table-fn" rid="TFN2">*</xref>
							</td>
              <td align="center">Medical consultation</td>
              <td align="center">10.00</td>
              <td align="center">3.04</td>
            </tr>
            <tr>
              <td align="center">Electrocardiogram</td>
              <td align="center">5.15</td>
              <td align="center">1.56</td>
            </tr>
            <tr>
              <td align="center">CRP</td>
              <td align="center">2.83</td>
              <td align="center">0.86</td>
            </tr>
            <tr>
              <td align="center">ESR</td>
              <td align="center">2.73</td>
              <td align="center">0.83</td>
            </tr>
            <tr>
              <td align="center">ASO</td>
              <td align="center">2.83</td>
              <td align="center">0.86</td>
            </tr>
            <tr>
              <td align="center">Oropharyngeal Culture</td>
              <td align="center">5.72</td>
              <td align="center">1.74</td>
            </tr>
            <tr>
              <td align="center">Transthoracic echocardiogram</td>
              <td align="center">39.64</td>
              <td align="center">12.03</td>
            </tr>
            <tr>
              <td align="center">Rapid antigen detection test for GAS</td>
              <td align="center">4.33</td>
              <td align="center">1.31</td>
            </tr>
            <tr>
              <td align="left" rowspan="4">Interventional procedures in RHD<xref ref-type="table-fn" rid="TFN2">*</xref>
							</td>
              <td align="center">Valve repair</td>
              <td align="center">6,061.70</td>
              <td align="center">1,840.33</td>
            </tr>
            <tr>
              <td align="center">Valve replacement</td>
              <td align="center">6,321.74</td>
              <td align="center">1,919.28</td>
            </tr>
            <tr>
              <td align="center">Multiple valve replacement</td>
              <td align="center">7,277.56</td>
              <td align="center">2,194.28</td>
            </tr>
            <tr>
              <td align="center">Percutaneous mitral valvuloplasty</td>
              <td align="center">1,739.19</td>
              <td align="center">528.01</td>
            </tr>
            <tr>
              <td align="left" rowspan="4">Hospitalization due to the consequences of RHD<xref ref-type="table-fn" rid="TFN2">*</xref>
							</td>
              <td align="center">Ischemic stroke</td>
              <td align="center">1,635.55</td>
              <td align="center">496.55</td>
            </tr>
            <tr>
              <td align="center">Heart failure</td>
              <td align="center">699.46</td>
              <td align="center">212.35</td>
            </tr>
            <tr>
              <td align="center">Atrial fibrillation</td>
              <td align="center">219.65</td>
              <td align="center">66.68</td>
            </tr>
            <tr>
              <td align="center">Infective endocarditis</td>
              <td align="center">880.00</td>
              <td align="center">267.68</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN1">
            <p>ARF:acute rheumatic fever; RHD: rheumatic heart disease; CRP: c-reactive protein; ESR: erythrocyte sedimentation rate; ASO: antistreptolysin O; GAS: group A &#946;-hemolytic Streptococcus.</p>
          </fn>
          <fn id="TFN2">
            <label>*</label>
            <p>Data from Jones Criteria, reviewed by the AHA.</p>
          </fn>
          <fn id="TFN3">
            <label>&#8224;</label>
            <p>The values in US dollars (US$) were obtained on February 8, 2018. One Brazilian Real (R$) was equivalent to US$ 0.3036. Source: The authors.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>With an average of 30,000 ARF cases per year in Brazil, in a hypothetical scenario based on the REMEDY study,<xref ref-type="bibr" rid="B16">16</xref> we would have the scenario shown in <xref ref-type="fig" rid="f2">Figure 2</xref>. According to this hypothesis, there would be 21.000 cases of RHD per year, which would lead to approximately 7.014 new patients with heart failure, 4.578 cases of atrial fibrillation, 1.491 cases of stroke, 8.904 cardiac surgeries and 840 cases of infective endocarditis.</p>
      <p>
        <fig id="f2">
          <label>Figure 2</label>
          <caption>
            <title>GAS: Group A &#946;-hemolytic Streptococcus. Hypothetical scenario based on the current panorama of rheumatic fever in Brazil, after crossing data from the Brazilian Institute of Geography and Statistics with data from the REMEDY study,16 showing the evolution of Acute Rheumatic Fever to Rheumatic Heart Disease, with their respective morbidities in numbers.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-113-03-0345-90141-gf02.jpg"/></fig>
      </p>
      <p>As shown in <xref ref-type="fig" rid="f3">Figure 3A</xref>, total expenditures with hospitalization in Brazil for RHD increased by 264% in the analyzed period, from R$ 23.077.356,65 (US$ 7.006.288,21) in 1998 to R$ 84.080.772,39 (US$ 25.526.924,01) in 2016. The costs in the analyzed period were recorded in 2013 (R$ 99.476.203,42 or US$ 30.200.975,35). Therefore, applying Holt&#8217;s Exponential Smoothing method, the predicted values for total costs related to RHD (<xref ref-type="fig" rid="f3">Figure 3</xref>B) were R$ 86.691.610,00 (US$ 26.319.572,79) and R$ 87.997.028,00 (US$ 26.715.897,70) for 2018 and 2019, respectively.</p>
      <p>
        <fig id="f3">
          <label>Figure 3</label>
          <caption>
            <title>Growth trends (A) and predicted values (B) for total costs with RHD. The model equation for the total costs with RHD (C) was RDH<sub>TC</sub> = &#8211;8346,31 + 4,19* Year. It should be noted that all trends were significant (p-value &lt; 0.050), evidencing the increasing trend of the series over time.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-113-03-0345-90141-gf03.jpg"/></fig>
      </p>
      <p>Considering this hypothetic scenario, where all the morbidities required at least one hospitalization and the regular values of cardiac surgeries, the expenses for the Brazilian public health system would have a minimum annual cost of R$ 56.726.131,10 (US$ 15.981.534,55), as shown in <xref ref-type="fig" rid="f4">Figure 4</xref>.</p>
      <p>
        <fig id="f4">
          <label>Figure 4</label>
          <caption>
            <title>Projection of estimated minimum annual costs in US dollars for Rheumatic Heart Disease morbidities. The final values were calculated based on the case estimates made in <xref ref-type="fig" rid="f2">Figure 2</xref>, multiplying by the values detailed in <xref ref-type="table" rid="t1">Table 1</xref>, taking into account only one procedure or one hospitalization for each patient over time.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-113-03-0345-90141-gf04.jpg"/></fig>
      </p>
      <p>Taking as reference the mortality rates from two diseases with a high global prevalence, breast cancer and prostate cancer, of which magnitude generated the preventive task force established by worldwide campaigns (Pink October and Blue November), RHD mortality behaves in a similar manner (<xref ref-type="fig" rid="f5">Figure 5</xref>). In this sense, we highlight that growth trends of RHD and BC are significant; however, there are no significant differences between them, which is demonstrated by the overlap of confidence intervals. Moreover, the PC trend was not statistically significant (p-value = 0.334) for the comparison of confidence intervals.</p>
      <p>
        <fig id="f5">
          <label>Figure 5</label>
          <caption>
            <title>Comparison between the increase of mortality rates for Rheumatic Heart Disease (RHD), Prostate Cancer (PC) and Breast Cancer (BC). According to the adjustment of a simple linear regression for each of the series, the trends for RDH (0.15 [0.12, 0.17]) and BC (0.14 [0.07, 0.22]) were significant (p-value &lt; 0.050) and did not show any significant difference, as the confidence intervals overlapped. The trend for PC (0.04 [-0.04; 0.12]) was not significant (p-value &gt; 0.050).</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-113-03-0345-90141-gf05.jpg"/></fig>
      </p>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>Rheumatic heart disease (RHD) is one of the leading noncommunicable diseases in low- and middle-income countries and accounts for up to 1.4 million deaths annually. There are few contemporary data systematically collected on disease characteristics, treatments, complications, and long-term outcomes in RHD patients.<xref ref-type="bibr" rid="B16">16</xref>
			</p>
      <p>Despite the magnitude of the problem, Brazil does not have a specific database for this pathology. Thus, because we did not have weekly or monthly data, it was not possible to statistically evaluate disease seasonality. Although these numbers may be underestimated by the lack of a health surveillance strategy during the entire studied period, it is observed that, each year, the number of deaths increases on average 16.94 units, as obtained from the model equation for the trend of the RHD mortality rate (<xref ref-type="fig" rid="f1">Figure 1C</xref> and <xref ref-type="fig" rid="f1">D</xref>). Indeed, ARF and RHD are included in the Brazilian list of preventable death causes for children under 5 years and for the age group of 5 to 75 years. The avoidable or reducible causes of death are defined as those totally or partially preventable by effective health care services, accessible at a certain place and time. Herein, this mortality rate refers to the overall Brazilian population, without distinction of age, with predictive values for 2019 at the magnitude of 8.53 for RHD and 2.68 for ARF, which are higher than the ones from 2017<xref ref-type="bibr" rid="B11">11</xref> (6.70 for RHD and 1.94 for ARF), representing an increase of 27.3% and 38.1% for the respective pathologies.</p>
      <p>The proposal of the World Health Organization (WHO), to reduce mortality from RHD and other NCDs (noncommunicable diseases) by 25% by the year 2025, requires an understanding of the contemporary characteristics and the use of proven interventions in patients living in endemic countries.<xref ref-type="bibr" rid="B19">19</xref> Taking into account our projections, this WHO proposal is far from our reality, which could be associated to the fact that ARF and RHD are diseases of poverty. Moreover, although ARF and RHD have largely disappeared from affluent parts of the world, they remain an important cause of morbidity and mortality in low-income countries and among marginalized sections of society in high-income countries.<xref ref-type="bibr" rid="B20">20</xref>
			</p>
      <p>These conditions had an impact on the costs of the National Health System, with a remarkable 264% increase in total expenditures with hospitalization for RHD from 1998 to 2016. Considering the current scenario, our predicted values point out the increment of 5.4% for the period from 2017 to 2018 and 1.5% from 2018 to 2019.</p>
      <p>The WHO defines secondary prophylaxis as &#8220;the continuous administration of specific antibiotics to patients with a previous attack of rheumatic fever, or well-documented rheumatic heart disease. The purpose is to prevent colonization or infection of the upper respiratory tract with GAS and the development of recurrent attacks of rheumatic fever&#8221;.<xref ref-type="bibr" rid="B4">4</xref> The internationally accepted dose for secondary prophylaxis with BPG in adults is 900 mg (1.2 million IU) intramuscularly. There is some uncertainty regarding the optimal frequency of administration; some studies suggest 2-weekly administration, whereas others report very good outcomes with a 3-weekly regimen<xref ref-type="bibr" rid="B21">21</xref> as established by the last Brazilian guideline.<xref ref-type="bibr" rid="B1">1</xref>
			</p>
      <p>Meanwhile, the value standardized by ANVISA's Drug Market Regulation Chamber for Benzathine Penicillin G is R$ 14.75 or US$ 4.48.<xref ref-type="bibr" rid="B15">15</xref> Considering the number of cases due to the evolution of ARF into RHD with its complications (<xref ref-type="fig" rid="f2">Figure 2</xref>) multiplied by the respective costs of procedures (<xref ref-type="table" rid="t1">Table 1</xref>) we reached the hypothetical value spent in 1 year (R$ 56,726,131.35 or U$ 15,981,534.55; <xref ref-type="fig" rid="f4">Figure 4</xref>). Thus, we highlight that this amount would be enough to carry out secondary prophylaxis of RHD (considered a BPG dose every 3 weeks) in 22,574 people for 10 years. Unfortunately, the low BPG accessibility is not a Brazilian problem, only. Minimal access to BPG was reported in almost all 24 countries in Africa, the Asia-Pacific region, and Central and South America in 2011,<xref ref-type="bibr" rid="B22">22</xref> with some respondents indicating no access to BPG at all. Of 39 respondents, 35% indicated that their BPG supply is inadequate to treat all of their patients using the recommended prophylaxis schedules.<xref ref-type="bibr" rid="B22">22</xref> Although there are no national data on access to BPG in Brazil, the concern about its lack of availability has increased in recent years.<xref ref-type="bibr" rid="B23">23</xref> This lack of an acceptable domestic supply of BPG is a significant problem in several global sites where RF/RHD is prevalent. Without consistent access to an inexpensive and high quality supply of BPG, children in areas with a high prevalence of RF/RHD will remain at risk of developing this crippling and life-threatening condition.<xref ref-type="bibr" rid="B22">22</xref>
			</p>
      <p>The increasing trend in the RHD and ARF mortality rates, with increments of 27.3% and 38.1% respectively (2017-2019), as well as the comparison between the total costs of the RHD morbidities and the use of BPG, indicates the need for public policies and programs for ARF / RHD control, leading to the early diagnosis and the prevention of disease development and its morbidities. Despite the lack of ARF/RHD control programs in Brazil, this prevention strategy has been already applied in many countries with positive responses, as evidenced by the following data. The 10-year program in Pinar del Rio (Cuba) dramatically reduced morbidity and premature mortality in children and young adults and was cost-effective.<xref ref-type="bibr" rid="B24">24</xref> A study carried out in Zambia has shown that understanding public perceptions and behaviors related to neck pain is critical to informing health programs aimed at eliminating new cases of RHD in endemic regions. This cross-sectional study found that pharyngitis is common among school children and adolescents, with women reporting significantly more episodes of sore throats than males. Parents/guardians have varying knowledge of the frequency of sore throats in their offspring, and management of pharyngitis may be suboptimal for many children, with more than one quarter receiving treatment without a qualified evaluation, providing a view of the need for public awareness campaigns aimed at reducing RHD,<xref ref-type="bibr" rid="B25">25</xref> which further reinforces the need for greater visibility regarding RHD in Brazil, with program implementation, considering the alarming perspectives of mortality shown in this article.</p>
      <p>This increase in mortality may be a matter of discussion considering the possible development of factors, such as better diagnosis, mortality notifications and BPG accessibility. Merely approximately 5% of all carriers of rheumatic fever have a symptomatic acute phase, whereas the majority of patients with severe cardiac rheumatic sequelae are diagnosed only in the final phase of the disease. In fact, these figures may be underestimated, and of these 5% symptomatic individuals, only about 5% need hospitalization,<xref ref-type="bibr" rid="B26">26</xref> according to DATASUS data. In Brazil, the PROVAR study<xref ref-type="bibr" rid="B27">27</xref> (the country's first large-scale screening program) was implemented in 2014 and revealed an echocardiographic prevalence of 42/1.000 in the preliminary assessment, contrasting with the IBGE prevalence of 7/1.000<xref ref-type="bibr" rid="B1">1</xref>. This shows that populational screening policies are needed to identify these asymptomatic patients, and it partially explains the increase in prevalence due to better diagnostic methods, but more studies are required to understand the real causes of this increase. The same study shows that although the prevalence of RHD has declined in high-income countries, lack of social and economic development and precarious primary prevention - especially in low- and middle-income countries - perpetuate an environment in which RHD remains endemic and with increasing trends. Moreover, the increased mortality rate is largely due to the stage at which the disease is diagnosed, a classic example being the young woman who discovers severe mitral stenosis only when an acute pulmonary edema is identified during pregnancy.<xref ref-type="bibr" rid="B28">28</xref>
			</p>
      <p>This progressive increase was also confirmed by another national study,<xref ref-type="bibr" rid="B27">27</xref> which justifies the greater availability of echocardiography, with more sensitive criteria, especially for subclinical RHD. In these subclinical cases, echocardiography plays a crucial role because it can establish the diagnosis or even raise suspicion of a possible case in those patients who are going through the last phase of the disease, from the acute manifestations of RFA to the last complications of RHD.<xref ref-type="bibr" rid="B29">29</xref>
			</p>
      <p>When analyzing our data on mortality from RHD, we see, to a certain extent, the results of non-diagnosed ARF and the cases that were adequately treated in the past. This gap can last 10 to 20 years.<xref ref-type="bibr" rid="B28">28</xref> Similarly, by implementing population screening measures to identify the individuals that occupy this gray area, the results will also come after at least a decade.<xref ref-type="bibr" rid="B29">29</xref>
			</p>
      <p>As in Brazil, the proportion of reports of ARF and RHD in the Pacific islands has increased in recent years, where GAS disease rates seem to be unstoppable.<xref ref-type="bibr" rid="B30">30</xref> In the same study, where the annual incidence of ARF was 155 per 100,000, a 41% increase was reported between 2004 and 2009, attributed to improved case detection and reporting of a record and a health program coordinator. However, raising awareness and case reporting is unlikely to account for the high rates of ongoing ARF in this population, as the disease became notifiable in Australia in 1996, an example that should be followed in Brazil, not only notifying hospitalized cases, but compulsorily notifying all cases, allowing greater prophylaxis use. Rates are likely to remain high because of the failure to adequately address socioeconomic determinants of health, increasing the already high rates of infection. Consequently, this remains a significant concern for public health that deserves more attention.</p>
      <p>RHD presentation (considering a 10-20 year latency), in the absence of a history of ARF, actually suggests that detection, accurate diagnosis and reporting of ARF remain below ideal. Contributing factors may include lack of training or awareness among health staff, transient health professional staff in remote areas, poor access to medical services, and lack of use of health services due to many factors.<xref ref-type="bibr" rid="B20">20</xref>
			</p>
      <p>Differences between echocardiographic criteria considerably affect the apparent prevalence of rheumatic heart disease in screening surveys, and emphasize the difficulties in the diagnosis of subclinical disease. Some might argue that there is a wide range of definitions of normality and that echocardiography screening might lead to over- diagnosis. Although controversial, evidence supports a link between mild valvular lesions, detected by echocardiography, and rheumatic heart disease, particularly the substantially higher case detection rates of such lesions in populations at risk for acute rheumatic fever.<xref ref-type="bibr" rid="B31">31</xref>
			</p>
      <p>Sustained control of rheumatic heart disease at a population level requires a high-functioning health system that meets the needs of vulnerable people. In high-income settings, rheumatic heart disease demonstrates persistent inequality.<xref ref-type="bibr" rid="B32">32</xref> For instance, indigenous Australians in the Northern Territory under 35 are 122 times more likely to have rheumatic heart disease than their non-indigenous peers in the same region, reinforcing that a greater focus on RHD prevention and control by strengthening the existing record-based programs (or the development of such programs where they are absent) in countries with high disease burden, improving primary care and raising awareness about ARF and RHD, is critical. Governments, as well as clinicians, should prioritize RHD control to ensure continued funding and recognition of large regional organizations.<xref ref-type="bibr" rid="B30">30</xref>
			</p>
      <p>In a challenging clinical setting characterized by high ARF/RHD rates, as in Brazil, an Australian study showed a significant improvement in care for people with ARF/RHD in association with the implementation of a continuous improvement quality (CQI) based on participatory research principles. Key findings include improvement in key clinical care indicators, including the administration of scheduled injections of BPG, scheduling injections at the recommended 4-week interval, and periodic review of documentation by a medical specialist, whereas significant improvements in record keeping were also related to ARF/RHD.<xref ref-type="bibr" rid="B33">33</xref>
			</p>
      <p>Another study carried out in Bangladesh showed that rheumatic fever and rheumatic heart disease are the most common cardiovascular diseases in young people &lt; 25 years of age and are important contributors to cardiovascular morbidity and mortality. It also shows that chronic RHD continues to prevail, and the real burden of disease may be much higher, indicating that large-scale epidemiological and clinical research is needed to formulate evidence-based national policies to address this important public health problem in the future.<xref ref-type="bibr" rid="B34">34</xref> As in Brazil, RHD continues to demand a high health and economic rate in African countries, but evidence-based prevention and treatment measures are currently underutilized.<xref ref-type="bibr" rid="B35">35</xref>
			</p>
      <p>An initial step for Brazil could be based on the report of the African Union Commission (AUC) Social Committee, which described actions that governments must take to eliminate ARF and eradicate RHD: (a) create prospective disease records in sentinel sites (b) decentralization of technical knowledge and technology for the diagnosis and management of ARF and RHD (including echocardiography), (c) establishment of national and regional centers of excellence for cardiac surgery, and (d) promoting international partnerships to mobilize resources and expertise.<xref ref-type="bibr" rid="B36">36</xref>
			</p>
      <p>Preventive task forces already well established, with the impact of worldwide campaigns, including Brazil, are Pink October and Blue November. We highlight that these two programs are related to prevention of breast cancer (BC) and prostate cancer (PC) mortality, of which magnitude is similar to that of ARF and RHD mortality.</p>
      <p>The Blue November began with a movement called <italic>Movember</italic> in Australia in 2003, taking advantage of the celebrations of the World Day to Fight Prostate Cancer, held on November 17, starting its activities in Brazil in 2008. Despite the support of several non-governmental entities, the movement, especially regarding its aspect related to prostate cancer, is repudiated by the Ministry of Health of Brazil and the National Cancer Institute due to the lack of scientific indications for the screening.<xref ref-type="bibr" rid="B37">37</xref>
			</p>
      <p>Pink October's history dates back to the last decade of the 20<sup>th</sup> century. In 1997, entities from the cities of Yuba and Lodi in the United States began effectively celebrating and promoting actions aimed at breast cancer prevention, called Pink October. All actions were and are directed towards the prevention and early diagnosis. From 1989-2015 (most recent data available), breast cancer mortality decreased by 39 percent (preventing more than 320,000 deaths).<xref ref-type="bibr" rid="B38">38</xref> The first initiative seen in Brazil in relation to the Pink October, was carried out in 2002, and is currently disseminated throughout the country, where there is the involvement of the health teams and the population.<xref ref-type="bibr" rid="B12">12</xref>
			</p>
      <p>The campaign against rheumatic heart disease needs a strong political will, driven by the awareness and effort of health professionals. The principles that underlie the control of this disease in high-income countries might not apply to developing countries. Where health care finances are very scarce and health is often provided by non-governmental organizations (NGOs), rheumatic heart disease might not be perceived as a priority.<xref ref-type="bibr" rid="B39">39</xref> Three successful approaches originating from Central America and the Caribbean, in different economic and political contexts, showed the efficiency of combined strategies consisting of education and primary and secondary prophylaxis.<xref ref-type="bibr" rid="B31">31</xref>
			</p>
      <p>Some initiatives in this sense have already been taken in Brazil, such as the PROVAR (Rheumatic Valvular Diseases Screening Program) program, being the first large-scale echocardiographic screening program in Brazil, using echocardiography to estimate the prevalence of latent RHD in asymptomatic children between 5 and 18 years of age attending public schools in the underserved areas of cities such as Belo Horizonte, Montes Claros and Bocai&#250;va, in the Brazilian state of Minas Gerais.<xref ref-type="bibr" rid="B40">40</xref>
			</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>The analysis of mortality rate trends in Brazil by ARF and RHD are alarming. At the advent of the new millennium, we know little about our real situation due to the lack of a more complete database aimed at this condition. The existing disease load may represent only the tip of the iceberg, since the analyzed data may be underestimated. On a large scale, preferably, national surveys and clinical studies should be conducted to determine the different aspects of RF and RHD in Brazil. The information added by this research would thus help to encourage the real need to formulate national policies to address this public health problem more efficiently in the future. Moreover - why not give a color to rheumatic fever?</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-group>
    <fn-group>
      <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>
    <fn-group>
      <fn fn-type="other">
        <p>
          <bold>Ethics approval and consent to participate</bold>
        </p>
        <p>This article does not contain any studies with human participants or animals performed by any of the authors.</p>
      </fn>
    </fn-group>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Febre Reum&#225;tica: Uma Doen&#231;a sem Cor</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-8293-8611</contrib-id>
          <name>
            <surname>Figueiredo</surname>
            <given-names>Estev&#227;o Tavares de</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-0502-4090</contrib-id>
          <name>
            <surname>Azevedo</surname>
            <given-names>Luciana</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1106-4176</contrib-id>
          <name>
            <surname>Rezende</surname>
            <given-names>Marcelo Lacerda</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2523-6111</contrib-id>
          <name>
            <surname>Alves</surname>
            <given-names>Cristina Garcia</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff3">
        <label>1</label>
        <institution content-type="original">Faculdade de Medicina de Ribeir&#227;o Preto (FMRP) da Universidade de S&#227;o Paulo (USP), Ribeir&#227;o Preto, SP - Brasil</institution>
      </aff>
      <aff id="aff4">
        <label>2</label>
        <institution content-type="original">Universidade Federal de Alfenas, Alfenas, MG - Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia:</bold> Estev&#227;o Tavares de Figueiredo Departamento de Cl&#237;nica M&#233;dica da FMRP - USP - Avenida Bandeirantes, 3900. CEP 14049-900, Ribeir&#227;o Preto, SP - Brasil E-mail: <email>etavaresdefigueiredo@gmail.com</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, An&#225;lise estat&#237;stica e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Figueiredo ET, Azevedo L, Rezende ML; Obten&#231;&#227;o de dados: Figueiredo ET, Alves CG; An&#225;lise e interpreta&#231;&#227;o dos dados e Reda&#231;&#227;o do manuscrito: Figueiredo ET, Azevedo L, Rezende ML, Alves CG.</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>O Brasil tem aproximadamente 30.000 casos de febre reum&#225;tica aguda (FRA) por ano. Um ter&#231;o das cirurgias cardiovasculares realizadas no pa&#237;s se deve &#224;s sequelas da doen&#231;a reum&#225;tica card&#237;aca (DRC), a qual &#233; um importante problema de sa&#250;de p&#250;blica.</p>
        </sec>
        <sec>
          <title>Objetivos:</title>
          <p>Analisar as s&#233;ries hist&#243;ricas de taxas de mortalidade e custos das doen&#231;as, projetando tend&#234;ncias futuras para oferecer novos dados que possam justificar a necessidade de implementa&#231;&#227;o de um programa de sa&#250;de p&#250;blica para FR.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Foi realizado um estudo transversal com an&#225;lise de s&#233;ries temporais a partir de dados do Sistema de Informa&#231;&#245;es Hospitalares do Brasil, de 1998 a 2016. Modelos de regress&#227;o linear simples e o m&#233;todo de suaviza&#231;&#227;o exponencial de Holt foram utilizados para modelar o comportamento das s&#233;ries e fazer previs&#245;es. Os resultados dos testes com um valor de p &lt;0,05 foram considerados estatisticamente significantes.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>A cada ano, o n&#250;mero de mortes por DRC aumentou em m&#233;dia 16,94 unidades, e a taxa de mortalidade por FRA aumentou em 215%. Houve um aumento de 264% nas despesas de hospitaliza&#231;&#227;o por DRC, e as taxas de mortalidade por DRC aumentaram 42,5% (p-valor &lt; 0,05). As taxas de mortalidade estimadas para FRA e DRC foram, respectivamente, 2,68 e 8,53 para 2019. O custo estimado para a DRC em 2019 foi de US$ 26.715.897,70.</p>
        </sec>
        <sec>
          <title>Conclus&#245;es:</title>
          <p>De acordo com a realidade brasileira, o gasto relativo a 1 ano de DRC seria suficiente para a profilaxia secund&#225;ria (considerando uma dose de penicilina G benzatina a cada 3 semanas) em 22.574 pessoas por 10 anos. Este estudo corrobora a necessidade de pol&#237;ticas p&#250;blicas de sa&#250;de direcionadas &#224; DRC.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Febre Reum&#225;tica</kwd>
        <kwd>Cardiopatia Reum&#225;tica</kwd>
        <kwd>Procedimentos Cir&#250;rgicos Cardiovasculares/mortalidade</kwd>
        <kwd>Hospitaliza&#231;&#227;o/economia</kwd>
        <kwd>Antibioticoprofilaxia/economia</kwd>
        <kwd>Pol&#237;ticas P&#250;blicas de Sa&#250;de</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>De acordo com o Instituto Brasileiro de Geografia e Estat&#237;stica (IBGE), o Brasil tem 10 milh&#245;es de casos de faringotonsilite a cada ano, levando a aproximadamente 30.000 casos de febre reum&#225;tica aguda (FRA).<xref ref-type="bibr" rid="B1">1</xref> A doen&#231;a reum&#225;tica card&#237;aca (DRC) tem baixa incid&#234;ncia nos pa&#237;ses desenvolvidos, com 0,1 a 0,4 casos/1.000 escolares nos EUA, enquanto no Brasil esses valores chegam a 7 casos/1.000 escolares, mostrando que est&#225; diretamente associada a fatores ambientais e socioecon&#244;micos.<xref ref-type="bibr" rid="B2">2</xref> Cerca de 70% dos pacientes com FRA evoluem para cardite, e um ter&#231;o das cirurgias cardiovasculares realizadas no Brasil s&#227;o decorrentes de sequelas da DRC.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref> A FR foi respons&#225;vel por um potencial de 5,1 milh&#245;es anos de vida perdidos ajustados por incapacidade (DALYs - do ingl&#234;s &#8220;<italic>disability-adjusted life years&#8221;</italic>), resultantes de 280.000 mortes em 2004, sendo a s&#233;tima e oitava causas de mortalidade e morbidade por doen&#231;as negligenciadas, respectivamente.<xref ref-type="bibr" rid="B5">5</xref>
				</p>
        <p>A febre reum&#225;tica &#233; uma doen&#231;a de natureza autoimune de rea&#231;&#227;o cruzada, desencadeada pela resposta do hospedeiro suscet&#237;vel ap&#243;s faringotonsilite, causada por <italic>Streptococcus</italic></p>
        <p>&#946;-hemol&#237;tico do Grupo A.<xref ref-type="bibr" rid="B6">6</xref><sup>-</sup><xref ref-type="bibr" rid="B8">8</xref> A implementa&#231;&#227;o do tratamento da faringotonsilite causada pelo <italic>Streptococcus</italic> &#946;-hemol&#237;tico do Grupo A, com Penicilina G Benzatina (PGB) em nove dias ap&#243;s o in&#237;cio dos sintomas, pode erradicar a infec&#231;&#227;o e evitar um primeiro surto de FR3 aguda ou um novo surto,<xref ref-type="bibr" rid="B9">9</xref> o que j&#225; era defendido pela OMS em 1955.<xref ref-type="bibr" rid="B10">10</xref> Infelizmente, o esperado parece n&#227;o ter sido alcan&#231;ado no Brasil, como mostram nossas an&#225;lises com dados do Sistema de Informa&#231;&#227;o Hospitalares (SIH) do Sistema &#218;nico de Sa&#250;de (SUS).<xref ref-type="bibr" rid="B11">11</xref>
				</p>
        <p>O SUS garante a todos no territ&#243;rio nacional o acesso universal e igualit&#225;rio aos cuidados e servi&#231;os de sa&#250;de. Assim, as pol&#237;ticas de sa&#250;de do Brasil incluem a&#231;&#245;es do setor p&#250;blico (SUS) e do setor privado (sa&#250;de suplementar ou planos de sa&#250;de privados), mais a&#231;&#245;es do setor privado no setor p&#250;blico (sa&#250;de complementar) e do setor p&#250;blico dentro do setor privado (regula&#231;&#227;o, inspe&#231;&#227;o, vigil&#226;ncia). Neste trabalho, apresentamos uma an&#225;lise de custo das a&#231;&#245;es e servi&#231;os de sa&#250;de relacionados &#224; FR e DRC, incididos sobre o SUS, isto &#233;, sob gest&#227;o p&#250;blica, que ocorre de maneira diferente daquela nos sistemas privados.</p>
        <p>Tendo em vista os dados apresentados e a aus&#234;ncia de um programa nacional de preven&#231;&#227;o de FR e DRC, o objetivo deste estudo foi analisar as s&#233;ries hist&#243;ricas de taxas de mortalidade e custos das doen&#231;as, projetando tend&#234;ncias futuras para oferecer novos dados que possam justificar a necessidade de implementar um programa de sa&#250;de p&#250;blica para a FR. Al&#233;m disso, estimamos os custos anuais das doen&#231;as e suas comorbidades no Brasil. Adicionalmente, a taxa de mortalidade por DRC foi comparada &#224;s taxas de mortalidade por c&#226;ncer de mama (CM) e de pr&#243;stata (CP), doen&#231;as que j&#225; possuem programas de sa&#250;de p&#250;blica implementados, como no caso dos programas Outubro Rosa<xref ref-type="bibr" rid="B12">12</xref> e Novembro Azul,<xref ref-type="bibr" rid="B13">13</xref> respectivamente.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Um estudo ecol&#243;gico transversal com an&#225;lise de s&#233;ries temporais foi desenvolvido para analisar as s&#233;ries hist&#243;ricas de taxas de mortalidade e custos da doen&#231;a, utilizando dados do SIH/SUS<xref ref-type="bibr" rid="B11">11</xref> de 1998 a 2016. O ano de 2017 n&#227;o foi inclu&#237;do neste estudo, pois os dados ainda estavam sujeitos a atualiza&#231;&#245;es.</p>
        <p>Para estimar o custo anual das doen&#231;as e suas comorbidades no Brasil, primeiramente determinamos os custos relacionados ao diagn&#243;stico de FRA, profilaxia prim&#225;ria e secund&#225;ria da DRC e os gastos p&#250;blicos associados com as consequ&#234;ncias da DRC, tais como procedimentos intervencionistas e hospitaliza&#231;&#245;es por insufici&#234;ncia card&#237;aca, fibrila&#231;&#227;o atrial, acidente vascular cerebral isqu&#234;mico e endocardite infecciosa. Para este prop&#243;sito, os dados foram obtidos conforme indicado a seguir: os procedimentos necess&#225;rios para o diagn&#243;stico de FRA e uso do Crit&#233;rio de Jones, revisado em intervalos irregulares pela American Heart Association (AHA), foram ajustados para a DRC. Para os custos de hospitaliza&#231;&#227;o, considerou-se o tempo m&#233;dio de hospitaliza&#231;&#227;o de 7 dias para Acidente Vascular Cerebral (AVC) isqu&#234;mico, insufici&#234;ncia card&#237;aca de 4 dias, 4 dias para fibrila&#231;&#227;o atrial e 17 dias para endocardite infecciosa.<xref ref-type="bibr" rid="B14">14</xref> Os dados relacionados ao custo dos procedimentos necess&#225;rios para o diagn&#243;stico de FRA/DRC e hospitaliza&#231;&#245;es devido &#224;s consequ&#234;ncias da DCR foram obtidos do banco de dados do Sistema de Gerenciamento da Tabela de Procedimentos, Medicamentos e OPM do SUS (SIGTAP)<xref ref-type="bibr" rid="B14">14</xref> e da C&#226;mara de Regula&#231;&#227;o do Mercado de Medicamentos (CMED), da Ag&#234;ncia Nacional de Vigil&#226;ncia Sanit&#225;ria (ANVISA).<xref ref-type="bibr" rid="B15">15</xref> Esses dados est&#227;o dispon&#237;veis no Sistema de Informa&#231;&#245;es Hospitalares - SIH/SUS - Sistema &#218;nico de Sa&#250;de do Brasil. Em segundo lugar, desenvolvemos um cen&#225;rio hipot&#233;tico baseado no atual panorama da febre reum&#225;tica no Brasil, cruzando dados do Instituto Brasileiro de Geografia e Estat&#237;stica com dados do estudo REMEDY,<xref ref-type="bibr" rid="B16">16</xref> com suas respectivas morbidades para estimar o n&#250;mero de casos. O estudo REMEDY envolveu 25 locais em 12 pa&#237;ses africanos, I&#233;men e &#205;ndia. Os pa&#237;ses foram agrupados em tr&#234;s categorias de renda: pa&#237;ses de baixa renda (Eti&#243;pia, Qu&#234;nia, Malawi, Ruanda, Uganda e Z&#226;mbia), pa&#237;ses de renda m&#233;dia-baixa (Egito, &#205;ndia, Mo&#231;ambique, Nig&#233;ria, Sud&#227;o e I&#234;men) e pa&#237;ses de renda m&#233;dia (Nam&#237;bia e &#193;frica do Sul).16 Os custos obtidos foram multiplicados pelo n&#250;mero de casos de infec&#231;&#227;o por <italic>Streptococcus</italic> &#946;-hemol&#237;tico do Grupo A (SBHGA), FRA, DRC, e morbidade por DRC.</p>
        <p>Al&#233;m disso, a taxa de mortalidade da DRC foi comparada com as taxas de mortalidade por c&#226;ncer de mama (CM) e de pr&#243;stata (CP), o que foi realizado considerando-se o per&#237;odo de 18 anos (1998 a 2016), utilizando dados do Sistema de Informa&#231;&#227;o sobre Mortalidade (SIM) do SUS - DATASUS,<xref ref-type="bibr" rid="B11">11</xref> respons&#225;vel pela manuten&#231;&#227;o dos dados de mortalidade no Brasil. Para esta compara&#231;&#227;o, uma regress&#227;o linear simples foi ajustada para cada caso (DRC, CP e CM).</p>
        <p>O presente trabalho utilizou apenas dados secund&#225;rios obtidos de fontes de acesso p&#250;blico. A aprova&#231;&#227;o deste estudo pelo Comit&#234; de &#201;tica em Pesquisa foi dispensada, conforme estabelecido na Resolu&#231;&#227;o 510 do Conselho Nacional de Sa&#250;de (CNS) de 7 de abril de 2016.</p>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>Para avaliar a tend&#234;ncia das s&#233;ries hist&#243;ricas, os modelos de regress&#227;o linear simples foram ajustados. Ao trabalhar com s&#233;ries temporais, &#233; comum encontrar problemas de heterocedasticidade e autocorrela&#231;&#227;o. Para lidar com esses problemas e permitir a realiza&#231;&#227;o de infer&#234;ncias v&#225;lidas para os modelos ajustados, bem como garantir a robustez dos modelos, utilizou-se o estimador HAC (<italic>Heteroskedasticity and Autocorrelation Consistent</italic>) para a matriz de covari&#226;ncia dos coeficientes estimados.<xref ref-type="bibr" rid="B17">17</xref> Para modelar o comportamento das s&#233;ries e fazer previs&#245;es, foi utilizado o m&#233;todo de suaviza&#231;&#227;o exponencial de Holt.<xref ref-type="bibr" rid="B18">18</xref> O programa R (vers&#227;o 3.2.4) foi utilizado para an&#225;lise estat&#237;stica. Os resultados dos testes com valor de p &lt; 0,05 foram considerados estatisticamente significantes. A limita&#231;&#227;o deste estudo foi a an&#225;lise do banco de dados do SIH (SUS),<xref ref-type="bibr" rid="B11">11</xref> cujos dados s&#227;o inseridos a cada dois meses ou mais, limitando a confian&#231;a apenas ao total dos dados anuais.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>As taxas de mortalidade por febre reum&#225;tica aguda (FRA) e doen&#231;a reum&#225;tica card&#237;aca (DRC) mostram um padr&#227;o crescente ao longo do per&#237;odo analisado (<xref ref-type="fig" rid="f6">Figura 1</xref>). A taxa de mortalidade por FRA subiu de 0,80 em 1998 para 2,52 em 2016, registrando um crescimento de 215%, com um aumento de 0,12 unidades, em m&#233;dia, a cada ano (<xref ref-type="fig" rid="f6">Figura 1A</xref>). A taxa de mortalidade por DRC foi de 5,77 em 1998, aumentando para 8,22 em 2016 (crescimento de 42,5%), mostrando um aumento m&#233;dio de 0,15 unidades por ano (<xref ref-type="fig" rid="f6">Figura 1C</xref>). Utilizando a suaviza&#231;&#227;o exponencial de Holt, foi poss&#237;vel realizar estimativas de mortalidade por FRA e DRC. Os valores previstos para a taxa de mortalidade por FRA para 2018 e 2019 foram, respectivamente, 2,59 e 2,68, enquanto os valores previstos para mortalidade por DRC foram 8,43 para 2018 e 8,53 para 2019.</p>
        <p>
          <fig id="f6">
            <label>Figura 1</label>
            <caption>
              <title>Tend&#234;ncias de crescimento e valor previsto para as taxas de mortalidade por febre reum&#225;tica aguda (FRA) e doen&#231;a reum&#225;tica card&#237;aca (DRC). A equa&#231;&#227;o modelo para a tend&#234;ncia da taxa de mortalidade por FRA (A) foi FRA<sub>MT</sub> = &#8211;237,79 + 0,12* Ano, enquanto para a tend&#234;ncia da taxa de mortalidade por DRC (C) a equa&#231;&#227;o foi DRC<sub>MT</sub> = &#8211;286,11 + 0,15* Ano. Deve-se notar que todas as tend&#234;ncias foram significativas (p-valor &lt; 0,050), demonstrando a tend&#234;ncia crescente da s&#233;rie ao longo do tempo.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-113-03-0345-90141-gf01-pt.jpg"/></fig>
        </p>
        <p>Embora esses n&#250;meros possam ser tido subestimados pela falta de uma estrat&#233;gia de vigil&#226;ncia em sa&#250;de, que ser&#225; discutida adiante, foram registrados 732 &#243;bitos em 2003, e ap&#243;s uma regress&#227;o linear (p-valor &lt; 0,005) de todo o per&#237;odo estudado, observa-se que o n&#250;mero de mortes aumentou, em m&#233;dia, 16,94 unidades a cada ano.</p>
        <p>Em rela&#231;&#227;o &#224;s an&#225;lises de custos, a <xref ref-type="table" rid="t2">Tabela 1</xref> mostra uma descri&#231;&#227;o detalhada dos custos obtidos para o diagn&#243;stico de FRA, os procedimentos intervencionistas mais comuns na DRC e os custos de hospitaliza&#231;&#227;o devido &#224;s consequ&#234;ncias da DCR, para um paciente hipot&#233;tico no contexto do sistema p&#250;blico de sa&#250;de brasileiro.</p>
        <table-wrap id="t2">
          <label>Tabela 1</label>
          <caption>
            <title>Descri&#231;&#227;o detalhada dos custos associados com o diagn&#243;stico de Febre Reum&#225;tica Aguda, bem como os custos dos procedimentos intervencionistas e interna&#231;&#245;es por Doen&#231;a Reum&#225;tica Card&#237;aca no contexto do sistema p&#250;blico de sa&#250;de do Brasil (valores estabelecidos para 2016)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" rowspan="2">Diagn&#243;stico e tratamento</th>
                <th align="center" rowspan="2">Procedimentos</th>
                <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">Custo individual por procedimento</th>
              </tr>
              <tr>
                <th align="center">(R$)</th>
                <th align="center">(US$)<sup><xref ref-type="table-fn" rid="TFN6">&#8224;</xref></sup></th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left" rowspan="8">Procedimentos necess&#225;rios para o diagn&#243;stico de FRA<xref ref-type="table-fn" rid="TFN5">*</xref>
								</td>
                <td align="center">Consulta m&#233;dica</td>
                <td align="center">10,00</td>
                <td align="center">3,04</td>
              </tr>
              <tr>
                <td align="center">Eletrocardiograma</td>
                <td align="center">5,15</td>
                <td align="center">1,56</td>
              </tr>
              <tr>
                <td align="center">PCR</td>
                <td align="center">2,83</td>
                <td align="center">0,86</td>
              </tr>
              <tr>
                <td align="center">VHS</td>
                <td align="center">2,73</td>
                <td align="center">0,83</td>
              </tr>
              <tr>
                <td align="center">ASO</td>
                <td align="center">2,83</td>
                <td align="center">0,86</td>
              </tr>
              <tr>
                <td align="center">Cultura orofar&#237;ngea</td>
                <td align="center">5,72</td>
                <td align="center">1,74</td>
              </tr>
              <tr>
                <td align="center">Ecocardiograma transtor&#225;cico</td>
                <td align="center">39,64</td>
                <td align="center">12,03</td>
              </tr>
              <tr>
                <td align="center">Teste r&#225;pido de detec&#231;&#227;o de ant&#237;genos para SBHGA</td>
                <td align="center">4,33</td>
                <td align="center">1,31</td>
              </tr>
              <tr>
                <td align="left" rowspan="4">Procedimentos intervencionistas na DRC<xref ref-type="table-fn" rid="TFN5">*</xref>
								</td>
                <td align="center">Reparo de v&#225;lvula</td>
                <td align="center">6.061,70</td>
                <td align="center">1.840,33</td>
              </tr>
              <tr>
                <td align="center">Substitui&#231;&#227;o de v&#225;lvula</td>
                <td align="center">6.321,74</td>
                <td align="center">1.919,28</td>
              </tr>
              <tr>
                <td align="center">Substitui&#231;&#227;o de m&#250;ltiplas v&#225;lvulas</td>
                <td align="center">7.277,56</td>
                <td align="center">2.194,28</td>
              </tr>
              <tr>
                <td align="center">Valvoplastia mitral percut&#226;nea</td>
                <td align="center">1.739,19</td>
                <td align="center">528,01</td>
              </tr>
              <tr>
                <td align="left" rowspan="4">Hospitaliza&#231;&#227;o devido &#224;s consequ&#234;ncias da DRC<xref ref-type="table-fn" rid="TFN5">*</xref>
								</td>
                <td align="center">Acidente vascular cerebral isqu&#234;mico</td>
                <td align="center">1.635,55</td>
                <td align="center">496,55</td>
              </tr>
              <tr>
                <td align="center">Insufici&#234;ncia card&#237;aca</td>
                <td align="center">699,46</td>
                <td align="center">212,35</td>
              </tr>
              <tr>
                <td align="center">Fibrila&#231;&#227;o atrial</td>
                <td align="center">219,65</td>
                <td align="center">66,68</td>
              </tr>
              <tr>
                <td align="center">Endocardite infecciosa</td>
                <td align="center">880,00</td>
                <td align="center">267,68</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN4">
              <p>FRA: febre reum&#225;tica aguda; DRC: doen&#231;a reum&#225;tica card&#237;aca; PCR: prote&#237;na C-reativa; VHS: velocidade de hemossedimenta&#231;&#227;o; ASO: antiestreptolisina O; SBHGA: Streptococcus &#946;-hemol&#237;tico do Grupo A.</p>
            </fn>
            <fn id="TFN5">
              <label>*</label>
              <p>Dados do Crit&#233;rio de Jones revisado pela AHA.</p>
            </fn>
            <fn id="TFN6">
              <label>&#8224;</label>
              <p>Os valores em d&#243;lares americanos (US$) foram cotados em 8 de fevereiro de 2018. Um Real (R$) brasileiro &#233; equivalente a US$ 0.3036. Fonte: Os autores.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Com uma m&#233;dia de 30.000 casos de FRA por ano no Brasil, em um cen&#225;rio hipot&#233;tico baseado no estudo REMEDY,<xref ref-type="bibr" rid="B16">16</xref> ter&#237;amos a situa&#231;&#227;o indicada na <xref ref-type="fig" rid="f7">Figura 2</xref>. Nesse cen&#225;rio hipot&#233;tico, ocorreriam 21.000 casos de DRC por ano, o que levaria a aproximadamente 7.014 novos pacientes com insufici&#234;ncia card&#237;aca, 4.578 casos de fibrila&#231;&#227;o atrial, 1.491 casos de acidente vascular cerebral, 8.904 cirurgias card&#237;acas e 840 casos de endocardite infecciosa.</p>
        <p>
          <fig id="f7">
            <label>Figura 2</label>
            <caption>
              <title>SBHGA: Streptococcus &#946;-hemol&#237;tico do Grupo A. Cen&#225;rio hipot&#233;tico baseado no atual panorama da febre reum&#225;tica no Brasil, cruzando dados do Instituto Brasileiro de Geografia e Estat&#237;stica com dados do estudo REMEDY,16 mostrando a evolu&#231;&#227;o da Febre Reum&#225;tica Aguda para Cardiopatia Reum&#225;tica, com suas respectivas morbidades em n&#250;meros.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-113-03-0345-90141-gf02-pt.jpg"/></fig>
        </p>
        <p>Como mostrado na <xref ref-type="fig" rid="f8">Figura 3A</xref>, o gasto total com interna&#231;&#227;o no Brasil por DRC aumentou 264% no per&#237;odo analisado, passando de R$23.077.356,65 (US$7.006.288,21) em 1998 para R$84.080.772,39 (US$25.526.924,01) em 2016. O valor dos custos do per&#237;odo analisado foi registrado em 2013 (R$99.476.203,42 ou US$30.200.975,35). Portanto, aplicando a Suaviza&#231;&#227;o Exponencial de Holt, os valores previstos para os custos totais da DRC (<xref ref-type="fig" rid="f8">Figura 3B</xref>) foram de R$86.691.610,00 (US$26.319.572,79) e R$87.997.028,00 (US$26.715.897,70) para os anos de 2018 e 2019, respectivamente.</p>
        <p>
          <fig id="f8">
            <label>Figura 3</label>
            <caption>
              <title>Tend&#234;ncias de crescimento (A) e valores previstos (B) para custos totais da DRC. A equa&#231;&#227;o do modelo para o custo total com DRC (C) foi DRC<sub>CT</sub> = &#8211;8346,31 + 4,19* Ano. Deve-se notar que todas as tend&#234;ncias foram significativas (p-valor &lt; 0,050), evidenciando a tend&#234;ncia crescente da s&#233;rie ao longo do tempo.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-113-03-0345-90141-gf03-pt.jpg"/></fig>
        </p>
        <p>Considerando esse cen&#225;rio hipot&#233;tico, em que todas as morbidades exigiam pelo menos uma hospitaliza&#231;&#227;o e os valores regulares das cirurgias card&#237;acas, os gastos para o sistema p&#250;blico de sa&#250;de brasileiro teriam um custo anual m&#237;nimo de R$56.726.131,10 (US$15.981.534,55), conforme mostrado na <xref ref-type="fig" rid="f9">Figura 4</xref>.</p>
        <p>
          <fig id="f9">
            <label>Figura 4</label>
            <caption>
              <title>Proje&#231;&#227;o dos custos anuais m&#237;nimos, estimados em d&#243;lares americanos, para morbidades por doen&#231;a reum&#225;tica card&#237;aca. Os valores finais foram calculados com base nas estimativas de casos, apresentadas na <xref ref-type="fig" rid="f7">Figura 2</xref>, multiplicando-se pelos valores detalhados na <xref ref-type="table" rid="t2">Tabela 1</xref>, levando em considera&#231;&#227;o apenas um procedimento ou uma hospitaliza&#231;&#227;o para cada paciente ao longo do tempo.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-113-03-0345-90141-gf04-pt.jpg"/></fig>
        </p>
        <p>Tomando como refer&#234;ncia as taxas de mortalidade de duas doen&#231;as com alta preval&#234;ncia global, c&#226;ncer de mama e c&#226;ncer de pr&#243;stata, cuja magnitude originou a for&#231;a-tarefa preventiva estabelecida por campanhas globais (Outubro Rosa e Novembro Azul), a mortalidade por DRC se comporta de maneira semelhante (<xref ref-type="fig" rid="f10">Figura 5</xref>). Nesse sentido, destacamos que as tend&#234;ncias de crescimento da DRC e do CM s&#227;o significativas; no entanto, n&#227;o h&#225; diferen&#231;a significativa entre essas tend&#234;ncias, o que &#233; demonstrado pela sobreposi&#231;&#227;o dos intervalos de confian&#231;a. Al&#233;m disso, a tend&#234;ncia do CP n&#227;o foi estatisticamente significativa (p-valor = 0,334) para compara&#231;&#227;o de intervalos de confian&#231;a.</p>
        <p>
          <fig id="f10">
            <label>Figura 5</label>
            <caption>
              <title>Compara&#231;&#227;o entre o crescimento das taxas de mortalidade por Doen&#231;a Reum&#225;tica Card&#237;aca (DRC), C&#226;ncer de Pr&#243;stata (CP), e C&#226;ncer de Mama (CM). De acordo com o ajuste de uma regress&#227;o linear simples para cada uma das s&#233;ries, as tend&#234;ncias para DRC (0,15 [0,12, 0,17]) e CM (0,14 [0,07, 0,22]) foram significativas (p &lt; 0,050) e n&#227;o apresentaram uma diferen&#231;a significante, uma vez que os intervalos de confian&#231;a apresentaram sobreposi&#231;&#227;o. A tend&#234;ncia para CP (0,04 [-0,04; 0,12]) n&#227;o foi significativa (p-valor &gt; 0,050).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-113-03-0345-90141-gf05-pt.jpg"/></fig>
        </p>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>A doen&#231;a reum&#225;tica card&#237;aca (DRC) &#233; uma das principais doen&#231;as n&#227;o transmiss&#237;veis em pa&#237;ses de baixa e m&#233;dia renda, e &#233; respons&#225;vel por at&#233; 1,4 milh&#227;o de mortes anualmente. H&#225; poucos dados recentes coletados sistematicamente sobre caracter&#237;sticas da doen&#231;a, tratamentos, complica&#231;&#245;es e desfechos de longo prazo em pacientes com DRC.<xref ref-type="bibr" rid="B16">16</xref>
				</p>
        <p>Apesar da magnitude do problema, o Brasil n&#227;o possui um banco de dados espec&#237;fico para essa patologia. Assim, por n&#227;o termos dados semanais ou mensais, n&#227;o foi poss&#237;vel avaliar estatisticamente a sazonalidade da doen&#231;a. Embora esses n&#250;meros possam estar subestimados pela falta de uma estrat&#233;gia de vigil&#226;ncia em sa&#250;de, durante todo o per&#237;odo estudado, observa-se que a cada ano o n&#250;mero de mortes aumenta, em m&#233;dia, 16,94 unidades, obtidas a partir da equa&#231;&#227;o do modelo para a tend&#234;ncia da taxa de mortalidade por DRC (<xref ref-type="fig" rid="f6">Figura 1C</xref> e <xref ref-type="fig" rid="f6">D</xref>). De fato, a FRA e a DRC est&#227;o inclu&#237;das na lista brasileira de causas de mortes evit&#225;veis para crian&#231;as menores de 5 anos e para a faixa et&#225;ria de 5 a 75 anos. As causas de morte evit&#225;veis ou redut&#237;veis s&#227;o definidas como aquelas total ou parcialmente evit&#225;veis por a&#231;&#245;es efetivas dos servi&#231;os de sa&#250;de, acess&#237;veis em um determinado local e tempo. No presente artigo, essa taxa de mortalidade refere-se &#224; popula&#231;&#227;o brasileira em geral, sem distin&#231;&#227;o de idade, com valores preditivos para 2019 na magnitude de 8,53 para DRC e 2,68 para FRA, maiores que os de 201711 (6,70 para DRC e 1,94 para FRA), representando um aumento de 27,3% e 38,1% para as respectivas patologias.</p>
        <p>A proposta da Organiza&#231;&#227;o Mundial da Sa&#250;de (OMS) de reduzir a mortalidade por DRC e outras DNTs (doen&#231;as n&#227;o transmiss&#237;veis) em 25% at&#233; o ano de 2025 requer uma compreens&#227;o das caracter&#237;sticas contempor&#226;neas e o uso de interven&#231;&#245;es comprovadas em pacientes que vivem em pa&#237;ses end&#234;micos.<xref ref-type="bibr" rid="B19">19</xref> Levando em conta nossas proje&#231;&#245;es, esta proposta da OMS se distancia de nossa realidade, o que poderia estar associado ao fato de que tanto a FRA como a DCR s&#227;o doen&#231;as da pobreza. Al&#233;m disso, apesar da FRA e DRC terem praticamente desaparecido nas partes mais afluentes do mundo, elas continuam sendo uma importante causa de morbidade e mortalidade em pa&#237;ses de baixa renda e entre setores marginalizados da sociedade em pa&#237;ses de alta renda.<xref ref-type="bibr" rid="B20">20</xref>
				</p>
        <p>Essas condi&#231;&#245;es t&#234;m um impacto nos custos do Sistema &#218;nico de Sa&#250;de, com aumento expressivo do gasto total com hospitaliza&#231;&#245;es por DRC em 264% de 1998 a 2016. Considerando o cen&#225;rio atual, nossos valores previstos apontam um incremento de 5,4% para o per&#237;odo de 2017 a 2018 e 1,5% de 2018 a 2019.</p>
        <p>A OMS define profilaxia secund&#225;ria como &#8220;a administra&#231;&#227;o cont&#237;nua de antibi&#243;ticos espec&#237;ficos a pacientes com um ataque anterior de febre reum&#225;tica, ou doen&#231;a reum&#225;tica card&#237;aca bem documentada. O objetivo &#233; prevenir a coloniza&#231;&#227;o ou infec&#231;&#227;o do trato respirat&#243;rio superior com SBHGA e o desenvolvimento de ataques recorrentes de febre reum&#225;tica&#8221;.<xref ref-type="bibr" rid="B4">4</xref> A dose internacionalmente aceita para profilaxia secund&#225;ria com PGB em adultos &#233; de 900 mg (1,2 milh&#245;es UI) por via intramuscular. H&#225; alguma incerteza sobre a frequ&#234;ncia ideal de administra&#231;&#227;o; alguns artigos sugerem sua administra&#231;&#227;o a cada duas semanas, outros relatam resultados muito bons em um regime de a cada tr&#234;s semanas,<xref ref-type="bibr" rid="B21">21</xref> conforme estabelecido pela &#250;ltima diretriz brasileira.<xref ref-type="bibr" rid="B1">1</xref>
				</p>
        <p>Enquanto isso, o valor padronizado pela C&#226;mara de Regula&#231;&#227;o do Mercado de Medicamentos (CMED) da ANVISA para a Penicilina G &#233; de R$ 14,75 ou US$ 4,48.15 Considerando o n&#250;mero de casos a partir da evolu&#231;&#227;o da FRA para DRC, com suas complica&#231;&#245;es (<xref ref-type="fig" rid="f7">Figura 2</xref>), multiplicados pelos respectivos custos dos procedimentos (<xref ref-type="table" rid="t2">Tabela 1</xref>), chegamos a um valor hipot&#233;tico gasto em 1 ano (R$ 56.726.131,35 ou US$ 15.981.534,55; <xref ref-type="fig" rid="f9">Figura 4</xref>). Assim, destacamos que essa quantidade seria suficiente para realizar a profilaxia secund&#225;ria da DRC (considerando uma dose de PGB a cada 3 semanas) em 22.574 pessoas por 10 anos. Infelizmente, a baixa acessibilidade &#224; PGB n&#227;o &#233; apenas um problema brasileiro. Um acesso m&#237;nimo &#224; PGB foi relatado em quase todos os 24 pa&#237;ses da &#193;frica, da regi&#227;o &#193;sia-Pac&#237;fico e Am&#233;rica Central e do Sul em 2011,22 com alguns entrevistados indicando nenhum acesso &#224; PGB. Dos 39 entrevistados, 35% indicaram que o suprimento de PGB &#233; inadequado para tratar todos os pacientes utilizando os esquemas recomendados de profilaxia.<xref ref-type="bibr" rid="B22">22</xref> Embora n&#227;o existam dados nacionais sobre o acesso &#224; PGB no Brasil, a preocupa&#231;&#227;o com a falta de disponibilidade vem aumentando nos &#250;ltimos anos.<xref ref-type="bibr" rid="B23">23</xref> Esta falta de uma oferta dom&#233;stica aceit&#225;vel de PGB &#233; um problema significativo em v&#225;rios locais pelo mundo onde a FR/DRC &#233; predominante. Sem acesso consistente a um suprimento barato e de alta qualidade da PGB, crian&#231;as em &#225;reas com alta preval&#234;ncia de FR/DRC permanecer&#227;o sob risco de desenvolver essa condi&#231;&#227;o incapacitante e potencialmente fatal.<xref ref-type="bibr" rid="B22">22</xref>
				</p>
        <p>A tend&#234;ncia crescente nas taxas de mortalidade por DCR e FRA, com incremento de 27,3% e 38,1%, respectivamente (2017-2019), assim como a compara&#231;&#227;o entre os custos totais das morbidades por DCR e o uso de PGB, evidenciam a necessidade de pol&#237;ticas p&#250;blicas e programas de controle de FRA/DRC que levem ao diagn&#243;stico precoce e &#224; preven&#231;&#227;o do desenvolvimento da doen&#231;a e suas morbidades. Apesar da falta de programas de controle de FRA/DRC no Brasil, essa estrat&#233;gia de preven&#231;&#227;o j&#225; foi aplicada em muitos pa&#237;ses com respostas positivas, como demonstrado pelos dados a seguir. O programa de 10 anos em Pinar del R&#237;o (Cuba) reduziu drasticamente a morbidade e a mortalidade prematura em crian&#231;as e adultos jovens com boa rela&#231;&#227;o custo-benef&#237;cio.<xref ref-type="bibr" rid="B24">24</xref> Um estudo realizado em Z&#226;mbia mostrou que compreender as percep&#231;&#245;es e comportamentos do p&#250;blico relacionados &#224; dor de garganta &#233; fundamental para informar os programas de sa&#250;de destinados a eliminar novos casos de DRC em regi&#245;es end&#234;micas. Esta pesquisa transversal descobriu que a faringite &#233; comum entre crian&#231;as em idade escolar e adolescentes, com mulheres relatando significativamente mais epis&#243;dios de dores de garganta do que os homens. Os pais/respons&#225;veis t&#234;m conhecimento variado da frequ&#234;ncia de dores de garganta em seus filhos, e o manejo de faringite pode ser abaixo do ideal para muitas crian&#231;as, com mais de um quarto recebendo tratamento sem uma avalia&#231;&#227;o qualificada, o que fornece uma vis&#227;o da necessidade de campanhas de conscientiza&#231;&#227;o p&#250;blica para a redu&#231;&#227;o da DRC,<xref ref-type="bibr" rid="B25">25</xref> refor&#231;ando ainda mais a necessidade de maior visibilidade para a DCR no Brasil com a implementa&#231;&#227;o do programa, tendo em vista as perspectivas alarmantes de mortalidade mostradas neste artigo.</p>
        <p>Podemos discutir sobre este aumento na mortalidade, considerando a poss&#237;vel evolu&#231;&#227;o de fatores, tais como o melhor diagn&#243;stico, notifica&#231;&#227;o de mortalidade e acessibilidade &#224; PGB. Apenas cerca de 5% de todos os portadores de febre reum&#225;tica t&#234;m uma fase aguda sintom&#225;tica, enquanto a maioria dos pacientes com sequelas reum&#225;ticas card&#237;acas graves &#233; diagnosticada apenas na fase final da doen&#231;a. Na realidade, esses n&#250;meros podem estar subestimados, e desses 5% sintom&#225;ticos, apenas cerca de 5% precisam de hospitaliza&#231;&#227;o,<xref ref-type="bibr" rid="B26">26</xref> de acordo com os dados do DATASUS. No Brasil, o estudo PROVAR<xref ref-type="bibr" rid="B27">27</xref> (o primeiro programa de triagem em larga escala do pa&#237;s) foi implementado em 2014, e revelou uma preval&#234;ncia ecocardiogr&#225;fica de 42/1.000 na an&#225;lise preliminar, contrastando com a preval&#234;ncia do IBGE de 7/1.000<xref ref-type="bibr" rid="B1">1</xref>. Isso demonstra que pol&#237;ticas populacionais de triagem s&#227;o necess&#225;rias para identificar esses pacientes assintom&#225;ticos, e explica, em parte, o aumento da preval&#234;ncia devido a melhores m&#233;todos diagn&#243;sticos; no entanto, s&#227;o necess&#225;rios mais estudos para entender as causas reais desse aumento. O mesmo estudo mostra que, embora a preval&#234;ncia de DRC tenha diminu&#237;do em pa&#237;ses de alta renda, a falta de desenvolvimento social e</p>
        <p>econ&#244;mico e a preven&#231;&#227;o prim&#225;ria ruim - especialmente em pa&#237;ses de baixa e m&#233;dia renda - perpetuam um ambiente no qual a DRC permanece end&#234;mica e com tend&#234;ncia de crescimento. Al&#233;m disso, o aumento da taxa de mortalidade ocorre em grande parte devido ao est&#225;gio no qual a doen&#231;a &#233; diagnosticada, sendo um exemplo cl&#225;ssico a jovem mulher que descobre estenose mitral grave somente quando um edema agudo de pulm&#227;o &#233; identificado durante a gravidez.<xref ref-type="bibr" rid="B28">28</xref>
				</p>
        <p>Esse aumento progressivo tamb&#233;m foi confirmado por outro estudo nacional,<xref ref-type="bibr" rid="B27">27</xref> o que justifica a maior disponibilidade da ecocardiografia, com crit&#233;rios mais sens&#237;veis, especialmente para a DRC subcl&#237;nica. Nesses casos subcl&#237;nicos, a ecocardiografia desempenha um papel crucial, pois pode estabelecer o diagn&#243;stico ou at&#233; mesmo levantar a suspeita de um poss&#237;vel caso naqueles pacientes que est&#227;o atravessando o &#250;ltimo per&#237;odo da doen&#231;a, desde as manifesta&#231;&#245;es agudas da FRA at&#233; as &#250;ltimas complica&#231;&#245;es da DRC.<xref ref-type="bibr" rid="B29">29</xref>
				</p>
        <p>Ao analisar nossos dados sobre a mortalidade por DRC observamos, at&#233; certo ponto, reflexos de FRA n&#227;o diagnosticada e n&#227;o tratada adequadamente no passado. Essa lacuna pode durar de 10 a 20 anos.<xref ref-type="bibr" rid="B28">28</xref> Da mesma forma, ao implementar medidas de triagem populacional para identificar os indiv&#237;duos que ocupam essa &#225;rea cinzenta, os resultados tamb&#233;m aparecer&#227;o depois de pelo menos uma d&#233;cada.<xref ref-type="bibr" rid="B29">29</xref>
				</p>
        <p>Assim como no Brasil, o n&#250;mero de notifica&#231;&#245;es de FRA e DRC nas ilhas do Pac&#237;fico aumentou nos &#250;ltimos anos, onde as taxas de infec&#231;&#227;o por SBHGA parecem ser imposs&#237;veis de evitar.<xref ref-type="bibr" rid="B30">30</xref> No mesmo estudo, onde a incid&#234;ncia anual de FRA &#233; de 155 por 100.000, um aumento de 41% foi relatado entre 2004 e 2009, fato atribu&#237;do a uma melhor detec&#231;&#227;o de casos, &#224; exist&#234;ncia de registros e um coordenador do programa de sa&#250;de. No entanto, &#233; improv&#225;vel que o aumento da conscientiza&#231;&#227;o e dos relatos de casos sejam os respons&#225;veis pelas altas taxas de FRA em curso nessa popula&#231;&#227;o, porque a doen&#231;a se tornou notific&#225;vel na Austr&#225;lia em 1996, um exemplo que deveria ser seguido pelo Brasil, n&#227;o apenas notificando casos de hospitaliza&#231;&#227;o, mas obrigatoriamente todos os casos, permitindo maior alcance da profilaxia. &#201; prov&#225;vel que as taxas permane&#231;am altas por causa de uma falha em abordar adequadamente os determinantes socioecon&#244;micos de sa&#250;de, ampliando as j&#225; altas taxas de infec&#231;&#227;o. Consequentemente, isso permanece como uma preocupa&#231;&#227;o significativa em termos de sa&#250;de p&#250;blica, que merece maior aten&#231;&#227;o.</p>
        <p>A ocorr&#234;ncia da DRC (considerando uma lat&#234;ncia de 10 a 20 anos), na aus&#234;ncia de um hist&#243;rico de FRA, de fato sugere que a detec&#231;&#227;o, o diagn&#243;stico preciso e a notifica&#231;&#227;o de FRA permanecem abaixo do ideal. Fatores que contribuem podem incluir a falta de treinamento ou conscientiza&#231;&#227;o dos integrantes da equipe de sa&#250;de, equipe profissional de sa&#250;de tempor&#225;ria em &#225;reas remotas, o acesso prec&#225;rio a servi&#231;os m&#233;dicos e a falta de uso de servi&#231;os de sa&#250;de devido a fatores diversos.<xref ref-type="bibr" rid="B20">20</xref>
				</p>
        <p>As diferen&#231;as entre os crit&#233;rios ecocardiogr&#225;ficos afetam consideravelmente a aparente preval&#234;ncia de cardiopatia reum&#225;tica nos estudos de triagem, enfatizando as dificuldades no diagn&#243;stico da doen&#231;a subcl&#237;nica. Alguns podem argumentar que existe uma ampla gama de defini&#231;&#245;es de normalidade, e que a triagem ecocardiogr&#225;fica pode levar ao sobrediagn&#243;stico. Embora controversas, as evid&#234;ncias suportam uma liga&#231;&#227;o entre les&#245;es valvares leves, detectadas pela ecocardiografia, e cardiopatia reum&#225;tica, particularmente as taxas de detec&#231;&#227;o de casos substancialmente mais altas dessas les&#245;es em popula&#231;&#245;es com risco de febre reum&#225;tica aguda.<xref ref-type="bibr" rid="B31">31</xref>
				</p>
        <p>O controle sustentado da doen&#231;a reum&#225;tica card&#237;aca a n&#237;vel populacional requer um sistema de sa&#250;de altamente funcional, que atenda &#224;s necessidades das pessoas vulner&#225;veis. Em ambientes de alta renda, a doen&#231;a reum&#225;tica card&#237;aca demonstra uma persistente desigualdade.32 Por exemplo, os ind&#237;genas australianos no Territ&#243;rio do Norte com menos de 35 anos s&#227;o 122 vezes mais propensos a ter doen&#231;as reum&#225;ticas card&#237;acas do que seus pares n&#227;o-ind&#237;genas na mesma regi&#227;o, refor&#231;ando que &#233; fundamental um foco maior na preven&#231;&#227;o e controle da DRC atrav&#233;s do fortalecimento de programas existentes baseados em registros (ou o desenvolvimento desses programas onde est&#227;o ausentes) em pa&#237;ses com alta carga de doen&#231;a, melhorando os cuidados prim&#225;rios e aumentando a conscientiza&#231;&#227;o sobre a FRA e a DCR. Os governos, assim como os m&#233;dicos, devem priorizar o controle da DRC para garantir o financiamento cont&#237;nuo e o reconhecimento de grandes organiza&#231;&#245;es regionais.<xref ref-type="bibr" rid="B30">30</xref>
				</p>
        <p>Em um cen&#225;rio cl&#237;nico desafiador caracterizado por altas taxas de FRA/DRC, como no Brasil, um estudo australiano mostrou uma melhora significativa no atendimento de pessoas com FRA/ DRC associada &#224; implementa&#231;&#227;o de um programa de melhoria cont&#237;nua de qualidade (CQI, do ingl&#234;s <italic>continuous improvement quality</italic>), com base em princ&#237;pios de pesquisa participativa. Os principais achados incluem melhoras nos principais indicadores de cuidados cl&#237;nicos, incluindo a administra&#231;&#227;o de inje&#231;&#245;es programadas de PGB, agendamento de inje&#231;&#245;es no intervalo recomendado de 4 semanas e revis&#227;o peri&#243;dica da documenta&#231;&#227;o por um m&#233;dico especialista, al&#233;m de melhoras significativas na manuten&#231;&#227;o de registros, que tamb&#233;m foram relacionados &#224; FRA/DRC.<xref ref-type="bibr" rid="B33">33</xref>
				</p>
        <p>Outro estudo realizado em Bangladesh mostra que a febre reum&#225;tica e as doen&#231;as reum&#225;ticas card&#237;acas s&#227;o as doen&#231;as cardiovasculares mais comuns em jovens com menos de 25 anos de idade, e contribuem de forma importante para a morbidade e mortalidade cardiovascular. Tamb&#233;m mostra que a DRC cr&#244;nica continua a prevalecer, e a carga real da doen&#231;a pode ser muito maior, indicando que pesquisas epidemiol&#243;gicas e cl&#237;nicas em larga escala s&#227;o necess&#225;rias para formular pol&#237;ticas nacionais, baseadas em evid&#234;ncias, para abordar esse importante problema de sa&#250;de p&#250;blica no futuro.<xref ref-type="bibr" rid="B34">34</xref> Como no Brasil, a DRC continua a exigir uma alta taxa de sa&#250;de e econ&#244;mica nos pa&#237;ses africanos, mas as medidas de preven&#231;&#227;o e tratamento baseadas em evid&#234;ncias s&#227;o atualmente subutilizadas.<xref ref-type="bibr" rid="B35">35</xref>
				</p>
        <p>Um passo inicial para o Brasil poderia ter como base o relat&#243;rio do Comit&#234; Social da Comiss&#227;o da Uni&#227;o Africana (AUC, <italic>African Union Commission - Social Committee</italic>), que descreveu as a&#231;&#245;es a serem adotadas pelos governos para eliminar a FRA e erradicar a DRC: (a) criar registros prospectivos de doen&#231;as nas &#225;reas sentinelas; (b) descentraliza&#231;&#227;o do conhecimento t&#233;cnico e tecnologia para diagn&#243;stico e manejo de FRA e DRC (incluindo ecocardiografia), (c) estabelecimento de centros nacionais e regionais de excel&#234;ncia para cirurgia card&#237;aca, e (d) promo&#231;&#227;o de parcerias internacionais para mobilizar recursos e conhecimento.<xref ref-type="bibr" rid="B36">36</xref>
				</p>
        <p>For&#231;as-tarefa preventivas j&#225; bem estabelecidas, com impacto de campanhas mundiais, inclusive no Brasil, s&#227;o as campanhas Outubro Rosa e Novembro Azul. Destacamos que esses dois programas est&#227;o relacionados &#224; preven&#231;&#227;o da mortalidade por CM (c&#226;ncer de mama) e CP (c&#226;ncer de pr&#243;stata), cuja magnitude se comporta de maneira semelhante &#224; mortalidade por FRA e DRC.</p>
        <p>O Novembro azul (<italic>Blue November</italic>) come&#231;ou com um movimento chamado <italic>Movember</italic> na Austr&#225;lia em 2003, aproveitando as comemora&#231;&#245;es do Dia Mundial de Combate ao C&#226;ncer de Pr&#243;stata, realizado em 17 de novembro, iniciando as atividades no Brasil em 2008. Apesar do apoio de v&#225;rias entidades n&#227;o-governamentais, o movimento, principalmente em seu aspecto relacionado ao c&#226;ncer de pr&#243;stata, &#233; repudiado pelo Minist&#233;rio da Sa&#250;de do Brasil e pelo Instituto Nacional do C&#226;ncer devido &#224; falta de indica&#231;&#245;es cient&#237;ficas para a triagem.</p>
        <p>A hist&#243;ria do Outubro Rosa (<italic>Pink October</italic>) remonta &#224; &#250;ltima d&#233;cada do s&#233;culo XX. Em 1997, entidades das cidades de Yuba e Lodi, nos Estados Unidos, come&#231;aram efetivamente a celebrar e promover a&#231;&#245;es voltadas para a preven&#231;&#227;o do c&#226;ncer de mama, chamado Outubro Rosa.<xref ref-type="bibr" rid="B37">37</xref> Todas as a&#231;&#245;es foram e s&#227;o direcionadas para a preven&#231;&#227;o e diagn&#243;stico precoce. De 1989 a 2015 (dados dispon&#237;veis mais recentes), a mortalidade por c&#226;ncer de mama diminuiu em 39% (evitando mais de 320.000 mortes).<xref ref-type="bibr" rid="B38">38</xref> A primeira iniciativa vista no Brasil em rela&#231;&#227;o ao Outubro Rosa foi em 2002, e atualmente tem uma grande dissemina&#231;&#227;o em todo o pa&#237;s, onde h&#225; o envolvimento de equipes de sa&#250;de e da popula&#231;&#227;o.<xref ref-type="bibr" rid="B12">12</xref>
				</p>
        <p>A campanha contra a doen&#231;a reum&#225;tica card&#237;aca precisa de uma vontade pol&#237;tica firme, impulsionada pela capacidade de conscientiza&#231;&#227;o e pelo esfor&#231;o dos profissionais de sa&#250;de. Os princ&#237;pios que fundamentam o controle dessa doen&#231;a em pa&#237;ses de alta renda podem n&#227;o se aplicar aos pa&#237;ses em desenvolvimento. Nesses pa&#237;ses, onde os recursos financeiros dos servi&#231;os de sa&#250;de s&#227;o significativamente escassos e a sa&#250;de muitas vezes &#233; fornecida por organiza&#231;&#245;es n&#227;o-governamentais (ONGs), a doen&#231;a reum&#225;tica card&#237;aca pode n&#227;o ser percebida como uma prioridade.<xref ref-type="bibr" rid="B39">39</xref> Tr&#234;s abordagens bem-sucedidas origin&#225;rias da Am&#233;rica Central e do Caribe, em diferentes contextos econ&#244;micos e pol&#237;ticos, mostraram a efici&#234;ncia das estrat&#233;gias combinadas que consistem em educa&#231;&#227;o e profilaxia prim&#225;ria e secund&#225;ria.<xref ref-type="bibr" rid="B31">31</xref>
				</p>
        <p>Algumas iniciativas nesse sentido j&#225; foram realizadas no Brasil, como o programa PROVAR (<italic>Rheumatic Valvular Diseases Screening Program</italic>), sendo o primeiro programa de triagem ecocardiogr&#225;fica em larga escala no Brasil, utilizando a ecocardiografia para estimar a preval&#234;ncia de DRC latente em crian&#231;as assintom&#225;ticas entre 5 e 18 anos frequentando escolas p&#250;blicas nas &#225;reas carentes das cidades de Belo Horizonte, Montes Claros e Bocai&#250;va, no estado brasileiro de Minas Gerais.<xref ref-type="bibr" rid="B40">40</xref>
				</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>A an&#225;lise das tend&#234;ncias da taxa de mortalidade no Brasil por FRA e DRC &#233; alarmante. No advento do novo mil&#234;nio, pouco sabemos sobre nossa situa&#231;&#227;o real pela falta de uma base de dados mais completa e direcionada para essa condi&#231;&#227;o. A carga de doen&#231;a existente pode representar apenas a ponta do iceberg, uma vez que os dados analisados podem estar subestimados. Em grande escala, de prefer&#234;ncia, pesquisas nacionais e estudos cl&#237;nicos devem ser conduzidos para determinar os diferentes aspectos da FR e da DRC no Brasil. A informa&#231;&#227;o acrescentada por esta pesquisa ajudaria, assim, a promover a necessidade real de formular pol&#237;ticas nacionais para abordar este problema de sa&#250;de p&#250;blica de forma mais eficiente no futuro. Al&#233;m disso - por que n&#227;o dar uma cor &#224; febre reum&#225;tica?</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
      </fn-group>
      <fn-group>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>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>
      <fn-group>
        <fn fn-type="other">
          <p>
            <bold>Aprova&#231;&#227;o &#233;tica e consentimento informado</bold>
          </p>
          <p>Este artigo n&#227;o cont&#233;m estudos com humanos ou animais realizados por nenhum dos autores.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
