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<journal-id journal-id-type="publisher-id">Front. Public Health</journal-id>
<journal-title>Frontiers in Public Health</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Public Health</abbrev-journal-title>
<issn pub-type="epub">2296-2565</issn>
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<article-id pub-id-type="doi">10.3389/fpubh.2025.1490252</article-id>
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<subject>Public Health</subject>
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<subject>Opinion</subject>
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<title-group>
<article-title>The Oropouche fever in Latin America: a hidden threat and a possible cause of microcephaly due to vertical transmission</article-title>
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<name><surname>Sansone</surname> <given-names>Nath&#x000E1;lia Mariana Santos</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<name><surname>Boschiero</surname> <given-names>Matheus Negri</given-names></name>
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<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
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<name><surname>Marques</surname> <given-names>Luiz Felipe Azevedo</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<name><surname>Marson</surname> <given-names>Fernando Augusto Lima</given-names></name>
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<aff id="aff1"><sup>1</sup><institution>Laboratory of Molecular Biology and Genetics, S&#x000E3;o Francisco University</institution>, <addr-line>Bragan&#x000E7;a Paulista, SP</addr-line>, <country>Brazil</country></aff>
<aff id="aff2"><sup>2</sup><institution>Laboratory of Clinical Microbiology and Genetics, S&#x000E3;o Francisco University</institution>, <addr-line>Bragan&#x000E7;a Paulista, SP</addr-line>, <country>Brazil</country></aff>
<aff id="aff3"><sup>3</sup><institution>LunGuardian Research Group&#x02014;Epidemiology of Respiratory and Infectious Diseases, S&#x000E3;o Francisco University</institution>, <addr-line>Bragan&#x000E7;a Paulista, SP</addr-line>, <country>Brazil</country></aff>
<aff id="aff4"><sup>4</sup><institution>Medical Resident in Infectious Disease at the Federal University of S&#x000E3;o Paulo</institution>, <addr-line>S&#x000E3;o Paulo, SP</addr-line>, <country>Brazil</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Andr&#x000E9; Ricardo Ribas Freitas, S&#x000E3;o Leopoldo Mandic School, Brazil</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Victoria Pando-Robles, National Institute of Public Health, Mexico</p>
<p>Ganeshwaran Mochida, Boston Children&#x00027;s Hospital and Harvard Medical School, United States</p></fn>
<corresp id="c001">&#x0002A;Correspondence: Fernando Augusto Lima Marson <email>fernandolimamarson&#x00040;hotmail.com</email>; <email>fernando.marson&#x00040;usf.edu.br.</email></corresp>
<fn fn-type="equal" id="fn001"><p>&#x02020;These authors have contributed equally to this work</p></fn>
<fn fn-type="other" id="fn002"><p>&#x02021;ORCID: Nath&#x000E1;lia Mariana Santos Sansone <ext-link ext-link-type="uri" xlink:href="https://orcid.org/0000-0003-4398-9245">orcid.org/0000-0003-4398-9245</ext-link></p></fn>
<fn fn-type="other" id="fn003"><p>Matheus Negri Boschiero <ext-link ext-link-type="uri" xlink:href="https://orcid.org/0000-0002-2866-391X">orcid.org/0000-0002-2866-391X</ext-link></p></fn>
<fn fn-type="other" id="fn004"><p>Luiz Felipe Azevedo Marques <ext-link ext-link-type="uri" xlink:href="https://orcid.org/0009-0008-5494-2171">orcid.org/0009-0008-5494-2171</ext-link></p></fn>
<fn fn-type="other" id="fn005"><p>Fernando Augusto Lima Marson <ext-link ext-link-type="uri" xlink:href="https://orcid.org/0000-0003-4955-4234">orcid.org/0000-0003-4955-4234</ext-link></p></fn>
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<pub-date pub-type="epub">
<day>26</day>
<month>03</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>13</volume>
<elocation-id>1490252</elocation-id>
<history>
<date date-type="received">
<day>07</day>
<month>10</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>03</day>
<month>03</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2025 Sansone, Boschiero, Marques and Marson.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Sansone, Boschiero, Marques and Marson</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license>
</permissions>
<kwd-group>
<kwd><italic>Culicoides paraensis</italic></kwd>
<kwd>dengue</kwd>
<kwd>diagnosis</kwd>
<kwd>epidemiology</kwd>
<kwd>pregnancy</kwd>
<kwd>viral infection</kwd>
<kwd>Zika virus</kwd>
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<meta-name>section-at-acceptance</meta-name>
<meta-value>Infectious Diseases: Epidemiology and Prevention</meta-value>
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</front>
<body>
<p>Dear Editor, Latin America (LATAM) is facing a severe outbreak of arbovirus, particularly dengue fever (<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B2">2</xref>). In addition, the cases of Oropouche fever (OF), a zoonotic disease caused by the Oropouche virus (OROV), are increasing (<xref ref-type="bibr" rid="B3">3</xref>). The OROV is a member of the <italic>Bunyaviridae</italic> family. Its viral genome is composed of three segments of negative-sense single-stranded ribonucleic acid (RNA). Previous outbreaks described between 2022 and 2024 were associated with viral rearrangements resulting in a reassortant virus, with genomic segments from different previously circulating strains (<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B5">5</xref>). Furthermore, a genomic rearrangement has been observed between the OROV and the Iquitos virus, both classified under the <italic>Orthobunyavirus oropoucheense</italic> species. This classification also included other species: Madre de Dios virus, Oropouche-like virus, and Perdoes virus (<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B5">5</xref>).</p>
<p>Transmitted mainly by the <italic>Culicoides paraensis</italic> midge, OF can also spread through other arthropods such as <italic>Aedes serratus, Culex quinquefasciatus</italic>, and <italic>Coquillettidia venezuelensis</italic> (<xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B7">7</xref>). First identified in Trinidad and Tobago in the 1950s, OF is endemic to the Amazon region and extends to umpteen Central and South American countries (<xref ref-type="bibr" rid="B6">6</xref>).</p>
<p>As of the 18th epidemiological week in 2024, LATAM reported 5,193 cases of OF, with Brazil accounting for 4,583 cases (88.3%)&#x02014;according to the Pan American Health Organization. Recent data from the Brazilian Ministry of Health show a dramatic increase to 6,976 cases by the 26th epidemiological week, marking an increase of 839.5% from 831 cases in 2023 (<xref ref-type="fig" rid="F1">Figures 1A</xref>, <xref ref-type="fig" rid="F1">B</xref>; <xref ref-type="fig" rid="F2">Figure 2</xref>). According to a recent Brazilian study, the OROV has been detected in all 26 states of Brazil in 2024. This contrasts with 2023, when the majority of cases were reported in the Amazon and Cerrado regions. Small and medium municipalities from the non-Amazon region were especially affected, with the frequency of cases 3 to 9 times higher than large municipalities (<xref ref-type="bibr" rid="B8">8</xref>). Please see the complete data in the <xref ref-type="fig" rid="F2">Figure 2</xref> and <xref ref-type="supplementary-material" rid="SM1">Supplementary Table 1</xref>.</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption><p>Epidemiology of Oropouche fever in Brazil. <bold>(A)</bold> Frequency of Oropouche fever in Brazil according to gender and age range. <bold>(B)</bold> Number of cases of Oropouche fever in Brazil according to epidemiological weeks. The image also presents the number of cases of Oropouche fever in Brazil registered in 2023. In 2024, data for 26 epidemiological weeks were computed, while in 2023, data for the entire year was collected. In 2023, 457, 178, 152, 43, and 1 cases occurred in the states of Amazonas, Acre, Roraima, Rond&#x000F4;nia, and Par&#x000E1;, respectively. <bold>(C)</bold> Brazilian states where cases of Oropouche fever were identified. Other states are presented the following number of cases&#x02014;Piau&#x000ED; (<italic>N</italic> = 19), Mato Grosso (<italic>N</italic> = 16), Pernambuco (<italic>N</italic> = 9), Amap&#x000E1; (<italic>N</italic> = 7), Cear&#x000E1; (<italic>N</italic> = 5), Paran&#x000E1; (<italic>N</italic> = 3), Maranh&#x000E3;o (<italic>N</italic> = 3), Tocantins (<italic>N</italic> = 1), and Mato Grosso do Sul (<italic>N</italic> = 1). Cases from Cear&#x000E1;, Paran&#x000E1;, and Mato Grosso do Sul are still being evaluated to determine the place of infection. <sup>a</sup>Three individuals did not have information about age or date of birth, <sup>b</sup>three individuals were probably infected in Bolivia. Data were collected from the website of the Brazilian Ministry of Health, the database of arboviruses. Emergency Operations Center, Weekly Report: Edition No. 21. The data are presented as the number of cases (N) and/or percentage (%).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fpubh-13-1490252-g0001.tif"/>
</fig>
<fig id="F2" position="float">
<label>Figure 2</label>
<caption><p>The data is presented as number of cases (N) and percentage (%). Immunoglobulin M (IgM).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fpubh-13-1490252-g0002.tif"/>
</fig>
<p>OF has also spread to non-endemic regions&#x02014;extra-Amazonian states&#x02014;where autochthonous cases have been reported (<xref ref-type="fig" rid="F1">Figure 1C</xref>). Factors such as global warming, deforestation, and flooding may exacerbate mosquito-borne disease outbreaks by modulating the life cycle of mosquitoes and promoting their proliferation (<xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B9">9</xref>). Furthermore, it is crucial to screen for viral genomic rearrangements, as these rearrangements in arboviruses have previously been associated with pandemics and human outbreaks.</p>
<p>The symptoms of OF are similar to those of other arboviruses such as dengue and chikungunya, complicating the diagnosis, and routine laboratory tests are scarce (<xref ref-type="bibr" rid="B6">6</xref>). The majority of cases are self-limiting, but serious complications such as meningitis and encephalitis can occur (<xref ref-type="bibr" rid="B6">6</xref>).</p>
<p>OF can lead to neurological issues such as those described before (<xref ref-type="bibr" rid="B7">7</xref>), but only the Zika virus has been definitively linked to microcephaly through vertical transmission (<xref ref-type="bibr" rid="B10">10</xref>). On 11 July 2024, the Brazilian Ministry of Health recommended increased surveillance for vertical transmission of the OROV (<xref ref-type="bibr" rid="B11">11</xref>). The Evandro Chagas Institute detected immunoglobulin M (IgM) antibodies to the OROV in serum and cerebrospinal fluid samples from four newborns with microcephaly, who tested negative for other arboviruses [Dengue, Chikungunya, Zika, and West Nile virus (<xref ref-type="bibr" rid="B12">12</xref>)]. Although the exact link between the OROV and microcephaly is not yet clear, recent findings include a case of fetal death at 30 weeks, with the virus detected in fetal organs, suggesting a potential for vertical transmission (<xref ref-type="bibr" rid="B12">12</xref>).</p>
<p>In addition to this discovery, Brazilian researchers traced a recent case series in which they evaluated infants who tested negative for other infectious diseases and congenital malformations, such as microcephaly and arthrogryposis, and their respective mothers for the presence of antibodies against the OROV. A total of 68 samples were collected: 65 from historical cases and 3 from 2024. Of the 68 samples, 6 (8.8%) from newborns exhibited a positive IgM reaction against OROV in the cerebral spinal fluid (6 cases). In addition, 4 cases presented a positive IgM reaction in the serum as well. Of the six newborn samples with a positive IgM reaction to OROV, one case at 44 days of age, had OROV RNA identified through real-time quantitative polymerase chain reaction analysis of cerebral spinal fluid. Furthermore, the patient, who died at 47 days of life, also tested positive for OROV RNA from pleural fluid and tissues from the brain, kidney, and lungs through the real-time quantitative polymerase chain reaction. In this particular case, several modifications of the brain macroscopically and microscopically were described, including necrotic and apoptotic changes in neurons, microglia and astrocytes, vacuolization, and tissue atrophy (<xref ref-type="bibr" rid="B13">13</xref>).</p>
<p>The Brazilian Ministry of Health has recommended intensifying the surveillance of pregnancies and newborns in cases of suspected arbovirus infections. This includes monitoring abortions, fetal deaths, and congenital neurological malformations, and collecting relevant biological samples. For protection, pregnant women should avoid areas prone to insects, use fine mesh screens, wear protective clothing, apply repellent, keep their homes clean, and follow local health guidelines if there are confirmed cases in their area (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B14">14</xref>).</p>
<p>Because it is an emerging arbovirus, in order to deal with the increase in OF cases, it is crucial to control mosquito proliferation and identify mosquito breeding sites (<xref ref-type="bibr" rid="B3">3</xref>). LATAM public health agents and governments should collaborate on health policies to promote OF education for better diagnosis and prevention. These efforts could manage local outbreaks, mitigate individual impact, and protect travelers from endemic areas. Continued research into the link between OF and microcephaly in newborns is also essential to understand their relationship. However, in addition to the measures taken to contain arboviruses, there is a need for continuous genomic surveillance for the OROV to monitor possible genomic rearrangements and optimize diagnostic methods. Currently, these methods still depend on complex machinery, especially in developing countries, thus avoiding underreporting. Finally, as occurred with the Zika virus, there is a need for cohort studies, especially prospective ones, with larger samples to assess the long-term complications for affected individuals and babies who may be born with microcephaly or other complications.</p>
</body>
<back>
<sec sec-type="author-contributions" id="s1">
<title>Author contributions</title>
<p>NS: Investigation, Resources, Validation, Visualization, Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. MB: Conceptualization, Investigation, Resources, Validation, Visualization, Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. LM: Conceptualization, Investigation, Methodology, Resources, Validation, Visualization, Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. FM: Conceptualization, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing.</p>
</sec>
<sec sec-type="funding-information" id="s2">
<title>Funding</title>
<p>The author(s) declare that financial support was received for the research and/or publication of this article. NS received a grant from the National Council for Scientific and Technological Development (in Portuguese <italic>Conselho Nacional de Desenvolvimento Cient</italic>&#x000ED;<italic>fico e Tecnol&#x000F3;gico</italic>&#x02014;CNPq), No. 88887.892875/2023-00. LA received a grant from the S&#x000E3;o Paulo Research Foundation (in Portuguese <italic>Funda&#x000E7;&#x000E3;o de Amparo &#x000E0; Pesquisa do Estado de S&#x000E3;o Paulo</italic>&#x02014;FAPESP), No. 2024/20061-9. The Article Processing Fee for the publication of this research was paid by the Higher Education Improvement Coordination (in Portuguese <italic>Coordena&#x000E7;&#x000E3;o de Aperfei&#x000E7;oamento de Pessoal de N</italic>&#x000ED;<italic>vel Superior</italic>&#x02014;CAPES, ROR No. 00x0ma614). For open access purposes, the authors have assigned the Creative Commons CC BY license to any accepted version of the article.</p>
</sec>
<sec sec-type="COI-statement" id="conf1">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="s3">
<title>Generative AI statement</title>
<p>The author(s) declare that no Generative AI was used in the creation of this manuscript.</p>
</sec>
<sec sec-type="disclaimer" id="s4">
<title>Publisher&#x00027;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec sec-type="supplementary-material" id="s5">
<title>Supplementary material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.frontiersin.org/articles/10.3389/fpubh.2025.1490252/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/fpubh.2025.1490252/full#supplementary-material</ext-link></p>
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