<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.0 20040830//EN" "journalpublishing.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="2.0" xml:lang="en" article-type="research-article"><front><journal-meta><journal-id journal-id-type="nlm-ta">JMIR Public Health Surveill</journal-id><journal-id journal-id-type="publisher-id">publichealth</journal-id><journal-id journal-id-type="index">9</journal-id><journal-title>JMIR Public Health and Surveillance</journal-title><abbrev-journal-title>JMIR Public Health Surveill</abbrev-journal-title><issn pub-type="epub">2369-2960</issn><publisher><publisher-name>JMIR Publications</publisher-name><publisher-loc>Toronto, Canada</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">v11i1e69048</article-id><article-id pub-id-type="doi">10.2196/69048</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Paper</subject></subj-group></article-categories><title-group><article-title>Balancing Human Mobility and Health Care Coverage in Sentinel Surveillance of Brazilian Indigenous Areas: Mathematical Optimization Approach</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name name-style="western"><surname>Oliveira</surname><given-names>Juliane Fonseca</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Vasconcelos</surname><given-names>Adriano O</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Alencar</surname><given-names>Andr&#x00EA;za L</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Cunha</surname><given-names>Maria C&#x00E9;lia S L</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Marcilio</surname><given-names>Izabel</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name name-style="western"><surname>Barral-Netto</surname><given-names>Manoel</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="fn" rid="equal-contrib1">*</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name name-style="western"><surname>P Ramos</surname><given-names>Pablo Ivan</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="equal-contrib1">*</xref></contrib></contrib-group><aff id="aff1"><institution>Center for Data and Knowledge Integration for Health, Gon&#x00E7;alo Moniz Institute, Funda&#x00E7;&#x00E3;o Oswaldo Cruz</institution><addr-line>Parque Tecnol&#x00F3;gico da Edf. Tecnocentro, R. Mundo, 121 - sala 315 - Trobogy</addr-line><addr-line>Salvador</addr-line><country>Brazil</country></aff><aff id="aff2"><institution>Luiz Coimbra Institute of Graduate and Engineering Research, Federal University of Rio de Janeiro</institution><addr-line>Rio de Janeiro</addr-line><country>Brazil</country></aff><aff id="aff3"><institution>Department of Computer Science, Federal Rural University of Pernambuco</institution><addr-line>Recife</addr-line><country>Brazil</country></aff><aff id="aff4"><institution>Bahiana School of Medicine and Public Health (EBMSP)</institution><addr-line>Salvador</addr-line><country>Brazil</country></aff><aff id="aff5"><institution>Medicine and Precision Public Health Laboratory, Gon&#x00E7;alo Moniz Institute, Funda&#x00E7;&#x00E3;o Oswaldo Cruz</institution><addr-line>Salvador</addr-line><country>Brazil</country></aff><contrib-group><contrib contrib-type="editor"><name name-style="western"><surname>Mavragani</surname><given-names>Amaryllis</given-names></name></contrib></contrib-group><contrib-group><contrib contrib-type="reviewer"><name name-style="western"><surname>Kim</surname><given-names>Hyunbum</given-names></name></contrib><contrib contrib-type="reviewer"><name name-style="western"><surname>Saadane</surname><given-names>Rachid</given-names></name></contrib></contrib-group><author-notes><corresp>Correspondence to Juliane Fonseca Oliveira, PhD, Center for Data and Knowledge Integration for Health, Gon&#x00E7;alo Moniz Institute, Funda&#x00E7;&#x00E3;o Oswaldo Cruz, Parque Tecnol&#x00F3;gico da Edf. Tecnocentro, R. Mundo, 121 - sala 315 - Trobogy, Salvador, 41745-715, Brazil, 55 71 3176 2357; <email>juliane.oliveira@fiocruz.br</email></corresp><fn fn-type="equal" id="equal-contrib1"><label>*</label><p>these authors contributed equally</p></fn></author-notes><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>1</day><month>4</month><year>2025</year></pub-date><volume>11</volume><elocation-id>e69048</elocation-id><history><date date-type="received"><day>20</day><month>11</month><year>2024</year></date><date date-type="rev-recd"><day>18</day><month>02</month><year>2025</year></date><date date-type="accepted"><day>19</day><month>02</month><year>2025</year></date></history><copyright-statement>&#x00A9; Juliane Fonseca Oliveira, Adriano O Vasconcelos, Andr&#x00EA;za L Alencar, Maria C&#x00E9;lia S L Cunha, Izabel Marcilio, Manoel Barral-Netto, Pablo Ivan P Ramos. Originally published in JMIR Public Health and Surveillance (<ext-link ext-link-type="uri" xlink:href="https://publichealth.jmir.org">https://publichealth.jmir.org</ext-link>), 1.4.2025. </copyright-statement><copyright-year>2025</copyright-year><license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Public Health and Surveillance, is properly cited. The complete bibliographic information, a link to the original publication on <ext-link ext-link-type="uri" xlink:href="https://publichealth.jmir.org">https://publichealth.jmir.org</ext-link>, as well as this copyright and license information must be included.</p></license><self-uri xlink:type="simple" xlink:href="https://publichealth.jmir.org/2025/1/e69048"/><abstract><sec><title>Background</title><p>Optimizing sentinel surveillance site allocation for early pathogen detection remains a challenge, particularly in ensuring coverage of vulnerable and underserved populations.</p></sec><sec><title>Objective</title><p>This study evaluates the current respiratory pathogen surveillance network in Brazil and proposes an optimized sentinel site distribution that balances Indigenous population coverage and national human mobility patterns.</p></sec><sec sec-type="methods"><title>Methods</title><p>We compiled Indigenous Special Health District (Portuguese: Distrito Sanit&#x00E1;rio Especial Ind&#x00ED;gena [DSEI]) locations from the Brazilian Ministry of Health and estimated national mobility routes by using the Ford-Fulkerson algorithm, incorporating air, road, and water transportation data. To optimize sentinel site selection, we implemented a linear optimization algorithm that maximizes (1) Indigenous region representation and (2) human mobility coverage. We validated our approach by comparing results with Brazil&#x2019;s current influenza sentinel network and analyzing the health attraction index from the Brazilian Institute of Geography and Statistics to assess the feasibility and potential benefits of our optimized surveillance network.</p></sec><sec sec-type="results"><title>Results</title><p>The current Brazilian network includes 199 municipalities, representing 3.6% (199/5570) of the country&#x2019;s cities. The optimized sentinel site design, while keeping the same number of municipalities, ensures 100% coverage of all 34 DSEI regions while rearranging 108 (54.3%) of the 199 cities from the existing flu sentinel system. This would result in a more representative sentinel network, addressing gaps in 9 of 34 previously uncovered DSEI regions, which span 750,515 km&#x00B2; and have a population of 1.11 million. Mobility coverage would improve by 16.8 percentage points, from 52.4% (4,598,416 paths out of 8,780,046 total paths) to 69.2% (6,078,747 paths out of 8,780,046 total paths). Additionally, all newly selected cities serve as hubs for medium- or high-complexity health care, ensuring feasibility for pathogen surveillance.</p></sec><sec sec-type="conclusions"><title>Conclusions</title><p>The proposed framework optimizes sentinel site allocation to enhance disease surveillance and early detection. By maximizing DSEI coverage and integrating human mobility patterns, this approach provides a more effective and equitable surveillance network, which would particularly benefit underserved Indigenous regions.</p></sec></abstract><kwd-group><kwd>representative sentinel surveillance</kwd><kwd>early pathogen detection</kwd><kwd>indigenous health</kwd><kwd>human mobility</kwd><kwd>surveillance network optimization</kwd><kwd>infectious disease surveillance</kwd><kwd>public health strategy</kwd><kwd>Brazil</kwd></kwd-group></article-meta></front><body><sec id="s1" sec-type="intro"><title>Introduction</title><p>Sentinel surveillance, which involves systematic and regular clinical sample collection for monitoring the emergence of infectious diseases across a network of sites, is a key component of public health strategies [<xref ref-type="bibr" rid="ref1">1</xref>]. Ideally, a sentinel surveillance network should be representative of the general population while also prioritizing high-risk subpopulations, such as Indigenous groups [<xref ref-type="bibr" rid="ref2">2</xref>-<xref ref-type="bibr" rid="ref5">5</xref>].</p><p>Major global sentinel networks include the Global Influenza Surveillance and Response System established by the World Health Organization, which operates across 127 countries [<xref ref-type="bibr" rid="ref6">6</xref>]; the European Influenza Surveillance Network [<xref ref-type="bibr" rid="ref7">7</xref>], which relies on reports from general practitioners to monitor flu activity; and SARInet plus (Severe Acute Respiratory Infections Network) in the Americas, which is coordinated by the Pan American Health Organization [<xref ref-type="bibr" rid="ref8">8</xref>]. These networks are essential for monitoring flu cases, detecting emerging respiratory viruses, guiding public health interventions and vaccine development, and standardizing global sentinel surveillance practices.</p><p>The effectiveness of and capability for early pathogen detection depend on local routine surveillance, which varies widely across regions and faces significant challenges [<xref ref-type="bibr" rid="ref6">6</xref>,<xref ref-type="bibr" rid="ref9">9</xref>]. In fact, despite the falling costs of genomic sequencing and advancements in metagenomics allowing for the monitoring of multiple pathogens and the identification of novel agents, low- and middle-income countries still struggle to scale up sentinel surveillance due to financial constraints, as well as a lack of political support for and investment in technological and scientific developments [<xref ref-type="bibr" rid="ref10">10</xref>-<xref ref-type="bibr" rid="ref13">13</xref>]. As a result, sentinel sites are often chosen based on convenience, leaving populations at high risk and important target regions, such as Indigenous communities, underserved. In this context, the use of alternative data streams to understand pathogen emergence and the likely pathways of disease spread may maximize the available information for improving the data-driven allocation of surveillance resources [<xref ref-type="bibr" rid="ref11">11</xref>,<xref ref-type="bibr" rid="ref13">13</xref>-<xref ref-type="bibr" rid="ref16">16</xref>]. In particular, this approach enables the incorporation of epidemiological intelligence into planning the target population and geographical location for sentinel clinical sample collection. Motivated by this, we integrated human mobility data with Indigenous population coverage to refine sentinel site selection in Brazil.</p><p>The boundaries between wild landscapes and human settlements have been increasingly blurred by climate change, agricultural and urban expansion, deforestation, and landscape fragmentation. These compounding factors heighten Indigenous communities&#x2019; vulnerability to infectious disease spillover, which can rapidly spread to urban areas [<xref ref-type="bibr" rid="ref17">17</xref>]. In addition, Brazilian Indigenous populations face significant barriers to health care access, limiting their awareness of circulating diseases and disproportionately increasing their disease burden [<xref ref-type="bibr" rid="ref2">2</xref>-<xref ref-type="bibr" rid="ref4">4</xref>,<xref ref-type="bibr" rid="ref18">18</xref>]. During the COVID-19 pandemic, the incidence of and mortality resulting from the disease among Indigenous and traditional people were higher when compared to those among the general population, highlighting the need for tailored public health strategies to address health disparities in these communities [<xref ref-type="bibr" rid="ref19">19</xref>-<xref ref-type="bibr" rid="ref22">22</xref>].</p><p>We recently showed how human mobility patterns can inform the redesign of existing sentinel networks to improve early pathogen detection [<xref ref-type="bibr" rid="ref13">13</xref>]. However, the high risk of pathogen emergence in Indigenous communities may remain undetected when relying solely on mobility data, potentially delaying the identification of health threats in these populations. To address this gap, we aimed to build and expand on our mobility-based model by explicitly incorporating the geographical distribution of Indigenous communities in Brazil. In particular, we aimed to provide an optimized list of cities that could serve as strategic candidate sites for early pathogen detection in Brazil, while also adding an equity component into sentinel planning.</p></sec><sec id="s2" sec-type="methods"><title>Methods</title><sec id="s2-1"><title>Data Sources</title><p>For our analyses, we collected data on cities within Brazilian Indigenous Special Health Districts (Portuguese: Distrito Sanit&#x00E1;rio Especial Ind&#x00ED;gena [DSEI]), which were obtained from the Brazilian Ministry of Health, along with mobility coverage data derived from the Ford-Fulkerson algorithm [<xref ref-type="bibr" rid="ref13">13</xref>,<xref ref-type="bibr" rid="ref23">23</xref>].</p><p>To ensure the practical applicability of our results, we also collected information on the composition of Brazil&#x2019;s current influenza sentinel surveillance network, which was obtained through direct communication with the Ministry of Health. We also incorporated a health attraction index, which quantifies a city&#x2019;s potential to attract individuals seeking health care services. This index, as estimated by the Brazilian Institute of Geography and Statistics [<xref ref-type="bibr" rid="ref24">24</xref>], categorizes cities based on their capacity to provide low-, medium-, and high-complexity health services, and its incorporation further refined our sentinel site selection process. The complete dataset is available in a GitHub directory [<xref ref-type="bibr" rid="ref25">25</xref>].</p></sec><sec id="s2-2"><title>Optimization Problem</title><p>To identify the most suitable sentinel sites for maximizing both human mobility coverage and the representation of DSEIs, we applied an optimization approach.</p><p>Brazil&#x2019;s 34 DSEIs are administrative regions designed to manage health activities for Indigenous territories in an ethnically and culturally sensitive manner. DSEIs encompass 1470 of Brazil&#x2019;s 5570 municipalities, with partial overlap in 46 others. Overlaps occur because Indigenous territories often span multiple municipalities or states, and DSEIs are designed to align with Indigenous geography rather than political borders. In our work, we considered a DSEI to be covered in the sentinel network if at least 1 municipality completely located within a DSEI was included in the design of the network.</p><p>To define mobility coverage, we constructed an intercity mobility network, which was represented as graph G=(V, E), where the set of nodes (V) corresponds to cities, and the set of links (E) represents movement frequencies between them. Using this network, we applied the Ford-Fulkerson algorithm [<xref ref-type="bibr" rid="ref13">13</xref>] to model potential disease spread pathways, identifying the most probable routes for pathogen transmission from a source city. This approach allowed us to determine key locations for early detection by analyzing how frequently cities appeared at different stages in these transmission paths. Further methodological details are available in our previously published paper [<xref ref-type="bibr" rid="ref13">13</xref>]. Based on the output of the Ford-Fulkerson algorithm, we defined a city&#x2019;s mobility coverage over another city, as follows: city A covers city B if n% of the most likely transmission paths originating from city B include city A as their first step; n is a value between 0 and 100, and when n=100, it is considered that city A fully covers city B.</p><p>To maximize mobility coverage while ensuring that all DSEI regions are represented, we formulated this as an optimization problem. Mathematically, we let  <italic>x<sub>i</sub></italic> be a binary variable, where  <italic>x<sub>i</sub></italic>=1 if city  <italic>i</italic> is selected for the sentinel network and  <italic>x<sub>i</sub></italic>=0 otherwise. Further, we let  <italic>&#x03C9;<sub>i</sub></italic> represent the mobility coverage weight of city <italic>i</italic>. Additionally, we let  <italic>R<sub>j</sub></italic> denote the set of cities within DSEI region  <italic>j</italic> and let  <italic>N</italic> be the total number of cities to be selected for the sentinel network. The optimization function was then defined as follows:</p><disp-formula id="equWL1"><mml:math id="eqn1"><mml:mstyle displaystyle="true" scriptlevel="0"><mml:mrow><mml:mstyle displaystyle="true" scriptlevel="0"><mml:mi>m</mml:mi><mml:mi>a</mml:mi><mml:mi>x</mml:mi><mml:mrow><mml:mo>(</mml:mo><mml:mrow><mml:munderover><mml:mo>&#x2211;</mml:mo><mml:mrow><mml:mi>i</mml:mi></mml:mrow><mml:mrow/></mml:munderover><mml:mtext>&#x00A0;</mml:mtext><mml:msub><mml:mi>&#x03C9;</mml:mi><mml:mrow><mml:mi>i</mml:mi></mml:mrow></mml:msub><mml:msub><mml:mi>x</mml:mi><mml:mrow><mml:mi>i</mml:mi></mml:mrow></mml:msub></mml:mrow><mml:mo>)</mml:mo></mml:mrow></mml:mstyle></mml:mrow></mml:mstyle></mml:math></disp-formula><p>subject to</p><p>1. <inline-formula><mml:math id="ieqn1"><mml:mstyle displaystyle="true" scriptlevel="0"><mml:mrow><mml:munder><mml:mo>&#x2211;</mml:mo><mml:mrow><mml:mi>i</mml:mi></mml:mrow></mml:munder><mml:msup><mml:mtext>&#x00A0;</mml:mtext><mml:mrow/></mml:msup><mml:msub><mml:mi>x</mml:mi><mml:mrow><mml:mi>i</mml:mi></mml:mrow></mml:msub><mml:mtext>&#x00A0;</mml:mtext><mml:mo>=</mml:mo><mml:mtext>&#x00A0;</mml:mtext><mml:mi>N</mml:mi></mml:mrow></mml:mstyle></mml:math></inline-formula>, that is, select <italic>N</italic> cities to compose the sentinel.</p><p>2. <inline-formula><mml:math id="ieqn2"><mml:mrow><mml:msubsup><mml:mo stretchy="false">&#x2211;</mml:mo><mml:mrow><mml:mi>j</mml:mi><mml:mo>&#x2208;</mml:mo><mml:msub><mml:mrow><mml:mi>R</mml:mi></mml:mrow><mml:mrow><mml:mi>j</mml:mi></mml:mrow></mml:msub></mml:mrow><mml:mrow/></mml:msubsup><mml:mrow/></mml:mrow><mml:msub><mml:mrow><mml:mi>x</mml:mi></mml:mrow><mml:mrow><mml:mi>j</mml:mi></mml:mrow></mml:msub><mml:mo>&#x2265;</mml:mo><mml:mi> </mml:mi><mml:mn>1</mml:mn><mml:mo>,</mml:mo><mml:mi> </mml:mi></mml:math></inline-formula>for all <inline-formula><mml:math id="ieqn3"><mml:mi>j</mml:mi><mml:mi> </mml:mi><mml:mo>&#x2208;</mml:mo><mml:mi> </mml:mi><mml:mfenced open="{" close="}" separators="|"><mml:mrow><mml:mn>1</mml:mn><mml:mo>,</mml:mo><mml:mi> </mml:mi><mml:mn>2</mml:mn><mml:mo>,</mml:mo><mml:mi> </mml:mi><mml:mo>.</mml:mo><mml:mo>.</mml:mo><mml:mo>.</mml:mo><mml:mo>,</mml:mo><mml:mi> </mml:mi><mml:mn>34</mml:mn></mml:mrow></mml:mfenced></mml:math></inline-formula>, that is, for each DSEI region <italic>j</italic>, at least 1 city in  <italic>R<sub>j</sub></italic> is selected.</p><p>The optimization problem was implemented in Python and solved by using the Python Universal Linear Programming library [<xref ref-type="bibr" rid="ref25">25</xref>].</p></sec><sec id="s2-3"><title>Practical Applicability</title><p>Brazil&#x2019;s flu sentinel network primarily requires sites in capital cities, with 1 site per 500,000 inhabitants, except in the south region, where 1 site is implemented for every 300,000 inhabitants, regardless of metropolitan status. Additionally, sample collection occurs in intensive care unit services that cover approximately 10% of the available intensive care unit beds in each municipality, ensuring coverage across age groups [<xref ref-type="bibr" rid="ref26">26</xref>].</p><p>To assess the practical applicability of our proposed sentinel network, we compared it with Brazil&#x2019;s existing flu sentinel network to evaluate improvements in mobility and Indigenous region coverage. We also assessed whether the newly identified cities serve as key access points for health care services across different levels of complexity. This evaluation reinforced that the proposed sentinel locations align with urban centers that attract individuals seeking health care, making them strategic candidates for genomic sample collection.</p></sec><sec id="s2-4"><title>Ethical Considerations</title><p>This study used publicly available secondary data sources. No personal data were collected or analyzed, ensuring the complete anonymity of all data. Ethical approval was not required, as the dataset consisted of anonymized, aggregated information, following resolutions 466/2012 and 510/2016 (article 1, sections III and V) from the National Health Council (Conselho Nacional de Sa&#x00FA;de), Brazil. All analyses were carried out in accordance with relevant ethical guidelines for data protection and research integrity.</p></sec></sec><sec id="s3" sec-type="results"><title>Results</title><p>The current network includes 310 sentinel sites in 199 municipalities, representing only 3.6% (199/5570) of the country&#x2019;s cities. To compose a more representative sentinel network for the country, we optimized the selection of 199 cities&#x2014;the same number considered in Brazil&#x2019;s current flu sentinel network. In the optimized network, we achieved 100% DSEI coverage by selecting the cities (87/199, 43.7%) that are fully inside of DSEI regions. In addition, 69.2% of the country&#x2019;s mobility pattern is covered by these cities, translating to 6,078,747 paths (of 8,780,046 total paths) originating from each city in the country.</p><p>In the current network, 53.8% (107/199) of the municipalities overlap 25 DSEIs (<xref ref-type="fig" rid="figure1">Figure 1</xref>). However, the following nine DSEIs lack any sentinel coverage: Altamira (Par&#x00E1;), Kayap&#x00F3; (Mato Grosso), Kayap&#x00F3; (Par&#x00E1;), M&#x00E9;dio Rio Purus (Amazonas), Parque Ind&#x00ED;gena do Xingu (Mato Grosso), Rio Tapaj&#x00F3;s (Par&#x00E1;), Vale do Javari (Amazonas), Xavante (Mato Grosso), and Yanomami (Roraima). These regions span more than 750,515 km&#x00B2; and are home to more than 1.11 million people. In addition, Brazil&#x2019;s current flu sentinel network covers only 52.4% (4,598,416 of 8,780,046 paths) of mobility patterns (considering air, road, and waterway transportation modes).</p><fig position="float" id="figure1"><label>Figure 1.</label><caption><p>Left: distribution of active surveillance sites within DSEIs in Brazil (2025). This map illustrates the current coverage of DSEIs by the national influenza surveillance network, highlighting the geographical distribution of sentinel sites across Indigenous regions. Colored areas represent DSEI regions according to the number of sentinel units. Right: proposed optimized list of municipalities within underserved Indigenous regions not currently covered by the Brazilian flu sentinel network, along with their corresponding mobility coverage. This list, which was generated from the optimization process, aims to improve DSEI coverage while incorporating Brazil&#x2019;s national human mobility patterns. The proposed cities guide resource allocation to enhance surveillance effectiveness in the country&#x2019;s underserved Indigenous areas. DSEI: Distrito Sanit&#x00E1;rio Especial Ind&#x00ED;gena.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="publichealth_v11i1e69048_fig01.png"/></fig><p>By rearranging 108 cities in Brazil&#x2019;s flu sentinel network&#x2014;keeping 91 cities that are already included in the current network&#x2014;we achieved 100% DSEI coverage and increased national mobility coverage by 16.8 percentage points (from 52.4% to 69.2%). <xref ref-type="fig" rid="figure1">Figure 1</xref> shows the list of municipalities that would ensure coverage for DSEIs without sentinel sites in Brazil&#x2019;s flu sentinel network.</p><p>Finally, we analyzed the movement of people seeking health care in the cities selected for the optimized sentinel network. None of the identified cities had a low health care attraction index. The majority (192/199, 96.5%) of cities serve as hubs for high-complexity health care services, while 3.5% (7/199) are classified as medium-complexity hubs. Among cities within DSEIs, 33% (29/87) have a high health care attraction index and are not currently covered by Brazil&#x2019;s flu sentinel network. Additionally, 67% (58/87) have a medium attraction index, with 4 lacking sentinel coverage.</p></sec><sec id="s4" sec-type="discussion"><title>Discussion</title><p>In this study, we present an optimized list of 199 cities that would enhance early pathogen detection by strategically balancing Indigenous area coverage and human mobility patterns. Our selection ensures 100% coverage of Indigenous regions through 87 key cities while also capturing 69.2% of the country&#x2019;s human mobility flows. Additionally, the feasibility of implementing sentinel surveillance in these locations is supported by their high health care attraction index, which indicates their role as hubs for complex health care services.</p><p>Our findings introduce a novel approach that integrates human mobility and Indigenous population coverage to optimally rearrange Brazil&#x2019;s current flu sentinel network locations for clinical sample collection. By focusing on the historically excluded Indigenous communities, the proposed approach aligns with expert recommendations to enhance surveillance in underserved areas [<xref ref-type="bibr" rid="ref2">2</xref>-<xref ref-type="bibr" rid="ref4">4</xref>,<xref ref-type="bibr" rid="ref10">10</xref>], thereby ultimately protecting vulnerable communities while improving Brazil&#x2019;s ability to detect and respond to emerging health threats.</p><p>By ensuring that all DSEIs are represented by at least 1 sentinel site, we addressed surveillance gaps in 9 previously uncovered regions that, collectively, are home to over 1 million people. This outcome is particularly significant, given the increased disease risks faced by Indigenous populations residing at the wildlife-urban interface. Our mobility-based optimization, which was combined with a restriction to 199 sentinel cities, reduced the number of cities within DSEIs when compared to Brazil&#x2019;s current flu sentinel network. This highlights the following two key considerations: (1) some DSEI regions covered in the existing network may be overserved, and (2) the total number of cities selected for sample collection may be insufficient to account for Brazil&#x2019;s geographic and epidemiological diversity, potentially limiting early pathogen detection. Nevertheless, maintaining or expanding routine sentinel surveillance is paramount to establishing a baseline of case incidence and tracking circulating viruses [<xref ref-type="bibr" rid="ref1">1</xref>], which enable the early detection of outbreaks and the introduction of emergent pathogens. For instance, the absence of baseline testing likely contributed to the delay in the recognition of the Zika virus outbreak in the Americas, which peaked in 2015 to 2016 but probably spread undetected since late 2013 [<xref ref-type="bibr" rid="ref27">27</xref>,<xref ref-type="bibr" rid="ref28">28</xref>].</p><p>The optimized sentinel network achieved 69.2% mobility coverage&#x2014;an improvement over Brazil&#x2019;s current flu sentinel network. This shows that incorporating Indigenous population criteria resulted in the optimized network&#x2019;s mobility coverage being only slightly lower than the 70% we reported [<xref ref-type="bibr" rid="ref13">13</xref>] for a network based solely on mobility patterns. This underscores the need to examine the key epidemiological priorities (which may include socioeconomic deprivation and regions with a high risk of climate-related disasters) that should be taken into account when designing a representative sentinel network for early pathogen detection, as these factors may impact coverage metrics. Consequently, identifying an optimal balance between the minimum number of cities required for sentinel surveillance and the diversity of epidemiological priorities remains a critical area for future research.</p><p>Establishing a sentinel surveillance network, including a pipeline from sample collection to laboratory analysis, demands substantial resources, especially in regions with limited infrastructure. To address this challenge, we strategically centered our focus around DSEIs&#x2014;an already in-place health administrative structure in Brazil that provides primary care to Indigenous populations and articulates with other networks in the Unified Health System to guarantee access to medium- and high-complexity services. Additionally, by evaluating the health attraction index and taking into account the outdated requirement for sentinel network implementation that was established by the Brazilian Ministry of Health [<xref ref-type="bibr" rid="ref26">26</xref>], we found that the newly selected cities already offer medium- to high-complexity health care services&#x2014;an indication that may support genomic sample collection. Leveraging this existing infrastructure not only facilitates routine surveillance but also strengthens overall health care capacity.</p><p>This work contributes novel insights to the literature by addressing the need for more effective selection of epidemiologically relevant criteria for early pathogen detection, while promoting a more equitable distribution of sentinel surveillance sites. To our knowledge, no previous study has explicitly optimized both underserved community coverage and human mobility patterns within a sentinel network framework. Existing research may only indicate standard criteria, such as gender, ethnicity, age, population coverage, and incidence of a specific disease [<xref ref-type="bibr" rid="ref1">1</xref>,<xref ref-type="bibr" rid="ref5">5</xref>,<xref ref-type="bibr" rid="ref10">10</xref>], or rely on a single data source with anticipatory potential [<xref ref-type="bibr" rid="ref29">29</xref>], without assessing whether these criteria are sufficient to truly maximize the chances of early threat detection. Our approach bridges this gap by offering a data-driven framework to enhance public health preparedness, and our findings may encourage the scientific community to discuss more about the importance of setting up and optimizing sentinel surveillance.</p><p>Our work has some limitations. Despite the significance of our findings, the data used in this study primarily identify the geographical regions encompassing Indigenous populations, without capturing other factors, such as climate-related risks or socioeconomic disparities, that may worsen these communities&#x2019; vulnerability to emerging new or unknown pathogens. Further research is needed to refine surveillance strategies tailored to these populations. Additionally, as we previously highlighted [<xref ref-type="bibr" rid="ref13">13</xref>], access to up-to-date mobility data remains a key challenge. Finally, we emphasize that this study represents a step toward more data-driven approaches in designing sentinel surveillance networks, demonstrating how different epidemiological criteria (exemplified by the two considered herein) can be integrated into the optimization process to enhance disease monitoring.</p><p>To conclude, our results indicate that our proposed framework can be used to effectively guide the optimization of sentinel site allocation, and the framework can be further validated for use during new emergencies or in the monitoring of flu syndrome in Brazil. Our results contribute to increasing the likelihood of early pathogen detection without requiring an expansion in the number of sentinel site locations that have already been put into place by the Brazilian Ministry of Health, thereby addressing the critical challenge of limited funding&#x2014;a well-documented barrier to improving global epidemiological surveillance, especially in low- and middle-income countries.</p></sec></body><back><ack><p>The findings reported are part of the Alert-Early System of Outbreaks with Pandemic Potential (&#x00C6;SOP) [<xref ref-type="bibr" rid="ref30">30</xref>], an initiative under development by Brazil's Funda&#x00E7;&#x00E3;o Oswaldo Cruz (Fiocruz) and the Federal University of Rio de Janeiro, with financial support from the Rockefeller Foundation's Health Initiative (grant 2023-PPI-007 awarded to MBN).</p></ack><notes><sec><title>Data Availability</title><p>All datasets collected and generated during this study, along with the corresponding code to 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