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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="1.3" xml:lang="en" article-type="research-article"><?properties open_access?><?properties manuscript?><processing-meta base-tagset="archiving" mathml-version="3.0" table-model="xhtml" tagset-family="jats"><restricted-by>pmc</restricted-by></processing-meta><front><journal-meta><journal-id journal-id-type="nlm-journal-id">101769019</journal-id><journal-id journal-id-type="pubmed-jr-id">49714</journal-id><journal-id journal-id-type="nlm-ta">Lancet Microbe</journal-id><journal-id journal-id-type="iso-abbrev">Lancet Microbe</journal-id><journal-title-group><journal-title>The Lancet. Microbe</journal-title></journal-title-group><issn pub-type="epub">2666-5247</issn></journal-meta><article-meta><article-id pub-id-type="pmid">38219756</article-id><article-id pub-id-type="pmc">11078024</article-id><article-id pub-id-type="doi">10.1016/S2666-5247(23)00392-0</article-id><article-id pub-id-type="manuscript">HHSPA1986353</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Influenza incidence, lineages, and vaccine effectiveness estimates in Lima, Peru, 2023</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Acevedo-Rodriguez</surname><given-names>Juan Gonzalo</given-names></name><aff id="A1">Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15102, Peru</aff></contrib><contrib contrib-type="author"><name><surname>Zamudio</surname><given-names>Carlos</given-names></name><aff id="A2">Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15102, Peru</aff></contrib><contrib contrib-type="author"><name><surname>Kojima</surname><given-names>Noah</given-names></name><aff id="A3">US Centers for Disease Control and Prevention, Atlanta, GA, USA</aff></contrib><contrib contrib-type="author"><name><surname>Krapp</surname><given-names>Fiorella</given-names></name><aff id="A4">Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15102, Peru</aff></contrib><contrib contrib-type="author"><name><surname>Tsukayama</surname><given-names>Pablo</given-names></name><aff id="A5">Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15102, Peru</aff></contrib><contrib contrib-type="author"><name><surname>Celi</surname><given-names>Victor Giancarlo Sal y Rosas</given-names></name><aff id="A6">Secci&#x000f3;n Matem&#x000e1;ticas, Departamento de Ciencias, Pontificia Universidad Cat&#x000f3;lica del Per&#x000fa;, Lima, Peru</aff></contrib><contrib contrib-type="author"><name><surname>Baldeon</surname><given-names>Dante</given-names></name><aff id="A7">Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15102, Peru</aff></contrib><contrib contrib-type="author"><name><surname>Neciosup-Vera</surname><given-names>Carmen Stefany</given-names></name><aff id="A8">Secci&#x000f3;n Matem&#x000e1;ticas, Departamento de Ciencias, Pontificia Universidad Cat&#x000f3;lica del Per&#x000fa;, Lima, Peru</aff></contrib><contrib contrib-type="author"><name><surname>Medina</surname><given-names>Carlos</given-names></name><aff id="A9">Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15102, Peru</aff></contrib><contrib contrib-type="author"><name><surname>Gonzalez-Lagos</surname><given-names>Elsa</given-names></name><aff id="A10">Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15102, Peru</aff></contrib><contrib contrib-type="author"><name><surname>Castro</surname><given-names>Laura</given-names></name><aff id="A11">US Centers for Disease Control and Prevention, Atlanta, GA, USA</aff></contrib><contrib contrib-type="author"><name><surname>Fowlkes</surname><given-names>Ashley</given-names></name><aff id="A12">US Centers for Disease Control and Prevention, Atlanta, GA, USA</aff></contrib><contrib contrib-type="author"><name><surname>Azziz-Baumgartner</surname><given-names>Eduardo</given-names></name><aff id="A13">US Centers for Disease Control and Prevention, Atlanta, GA, USA</aff></contrib><contrib contrib-type="author"><name><surname>Gotuzzo</surname><given-names>Eduardo</given-names></name><aff id="A14">Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15102, Peru</aff></contrib><on-behalf-of>on behalf of the PISAAC working group</on-behalf-of></contrib-group><author-notes><corresp id="CR1">
<email>eduardo.gotuzzo@upch.pe</email>
</corresp></author-notes><pub-date pub-type="nihms-submitted"><day>25</day><month>4</month><year>2024</year></pub-date><pub-date pub-type="ppub"><month>4</month><year>2024</year></pub-date><pub-date pub-type="epub"><day>11</day><month>1</month><year>2024</year></pub-date><pub-date pub-type="pmc-release"><day>08</day><month>5</month><year>2024</year></pub-date><volume>5</volume><issue>4</issue><fpage>e308</fpage><lpage>e309</lpage><permissions><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/" specific-use="textmining" content-type="ccbyncndlicense">https://creativecommons.org/licenses/by-nc-nd/4.0/</ali:license_ref><license-p>This is an open access article under the CC BY-NC-ND license (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by-nc-nd/4.0/">http://creativecommons.org/licenses/by-nc-nd/4.0/</ext-link>).</license-p></license></permissions></article-meta></front><body><p id="P1">Characterisation of influenza viruses in the southern hemisphere can guide local response and provide insights to northern hemisphere jurisdictions about their upcoming influenza season.<sup><xref rid="R1" ref-type="bibr">1</xref>,<xref rid="R2" ref-type="bibr">2</xref></sup> Here, we present the information on 2023 end of influenza season in the southern hemisphere about influenza lineages, incidence of medically attended, laboratory-confirmed influenza cases, and influenza vaccine effectiveness (VE) against the antigen from surveillance clinics and a hospital in San Juan de Lurigancho and San Martin de Porres, the two most populated districts of Peru.</p><p id="P2">From Jan 1 to Sept 30, 2023, surveillance nurses sought individuals with COVID-19-like illness (CLI) of any age seeking care at outpatient sentinel sites between Monday and Saturday. CLI was defined as presenting with at least two of the following symptoms or signs&#x02014;fever, chills, rigors, myalgia, headache, or sore throat for not more than 7 days from illness onset.<sup><xref rid="R3" ref-type="bibr">3</xref></sup> On March 7, 2023, the nurses expanded their search to CLI cases hospitalised for not more than 72 h at Cayetano Heredia National Hospital.</p><p id="P3">Nurses obtained written consent to survey and swab CLI cases. Enrolled participants provided information on pre-existing conditions and influenza vaccination status. Individuals targeted for vaccination by Peru and vaccinated between Jan and Sept 2022, more than 14 days before enrolment, were considered vaccinated (<xref rid="SD2" ref-type="supplementary-material">appendix p 1</xref>).</p><p id="P4">Nasopharyngeal swabs were obtained from individuals at the clinic. Anterior nasal and oral swabs were obtained from hospitalised patients. Specimens were tested for influenza and SARS-CoV-2 via multiplex quantitative PCR (qPCR).<sup><xref rid="R4" ref-type="bibr">4</xref></sup> Positive specimens with a cycle threshold value of 25 or less were sequenced by the Illumina Respiratory Virus Panel (Illumina, San Diego, CA, USA).<sup><xref rid="R5" ref-type="bibr">5</xref></sup></p><p id="P5">We estimated the incidence of laboratory-confirmed influenza CLI by dividing the number of qPCR detections by the population assigned to the sentinel clinics by the Ministry of Health (ie, 91 801), adjusting for the proportion of CLI cases seeking care at sentinel versus other clinics in San Juan de Lurigancho and the proportion of CLI enrolled versus not enrolled (<xref rid="SD2" ref-type="supplementary-material">appendix pp 2</xref>&#x02013;<xref rid="SD2" ref-type="supplementary-material">3</xref>).</p><p id="P6">We calculated VE against medically attended influenza using a test-negative design.<sup><xref rid="R6" ref-type="bibr">6</xref></sup> For this analysis, influenza cases were defined as qPCR influenza-positive CLI, whereas controls were defined as qPCR influenza-negative and SARS-CoV-2-negative CLI. Age, any pre-existing condition, and calendar year quarter were used to adjust VE. Surveillance activities were approved by the institutional review board of Universidad Peruana Cayetano (PRISA repository: EI0002439 and EI00002991) and the US Centers for Disease Control and Prevention as non-research (0900f3eb81ecbe9f and 0900f3eb820d72ac).</p><p id="P7">During the surveillance period, 8688 individuals sought clinic care for respiratory illness. Surveillance nurses screened 1951 (22&#x000b7;5%) individuals, of whom 1196 (61&#x000b7;3%) met the CLI criteria and 732 (61&#x000b7;2%) were enrolled and swabbed (<xref rid="SD2" ref-type="supplementary-material">appendix p 4</xref>). Influenza was detected in 106 (14&#x000b7;5%) participants; 79 (75%) had type A influenza and 27 (25%) B influenza (<xref rid="SD2" ref-type="supplementary-material">appendix pp 5</xref>,<xref rid="SD2" ref-type="supplementary-material">7</xref>). Most (34 [87%] of 39) specimens with a cycle threshold value of 25 or less were sequenced and 30 (88%) of 34 belonged to influenza A(H1N1)pdm09 clade 6B.1A.5a.2a and 4 (12%) belonged to influenza A(H3N2) clade 3C.2a1b.2a.2a.3. No influenza B/Yamagata lineage viruses were identified. From March 7 to Sept 30, 2023, 12 (3&#x000b7;5%) of 342 hospitalised CLI cases were qPCR-positive for influenza type A, none were type B.</p><p id="P8">The cumulative incidence of influenza CLI was 72&#x000b7;2 (95% CI 57&#x000b7;9 to 90&#x000b7;0) per 1000 population (<xref rid="SD2" ref-type="supplementary-material">appendix p 6</xref>); for participants enrolled at the clinic, 77 (10&#x000b7;5%) were vaccinated, 632 (86&#x000b7;3%) were not vaccinated, and 23 (3&#x000b7;1%) could not recall their vaccination status. The adjusted VE against medically attended influenza CLI at clinics was 51&#x000b7;8% (95% CI &#x02212;5&#x000b7;7 to 78&#x000b7;0).</p><p id="P9">During the 2023 influenza season in the southern hemisphere, we identified a higher incidence of influenza than that estimated by pre-COVID-19 Peruvian cohorts using the more specific influenza-like illness case definition&#x02014;ie, 44 per 1000 person-years (95% CI 42&#x000b7;0 to 46&#x000b7;0).<sup><xref rid="R7" ref-type="bibr">7</xref></sup> Only one in ten enrolled participants from the clinic were vaccinated against seasonal influenza. Vaccinated individuals showed a 50% reduction in medically attended illnesses. The A/Victoria/2570/2019 (H1N1)pdm09-like virus antigen in the southern hemisphere vaccine formulation was effective in protecting against the predominant A(H1N1)pdm09 clade 6B.1A.5a.2a virus. Southern hemisphere 2023 influenza VE protection was similar to that of southern hemisphere 2022,<sup><xref rid="R1" ref-type="bibr">1</xref>,<xref rid="R2" ref-type="bibr">2</xref></sup> US 2022&#x02013;23, and early southern hemisphere 2023 seasons.<sup><xref rid="R8" ref-type="bibr">8</xref></sup></p><p id="P10">Our findings have some limitations. Despite using a sensitive case definition, we probably missed non-respiratory influenza illnesses and underestimated influenza incidence. We relied on self-reported vaccination status and could not fully adjust our VE models for parameters associated with individuals&#x02019; propensity to seek vaccination and care. Moreover, only half of the specimens had a cycle threshold value of 25 or less, and we might have missed emerging clades at the time of the evaluation.</p><p id="P11">Our findings suggest that mostly unvaccinated people sought care early during the southern hemisphere season for illnesses that were predominantly attributable to influenza A(H1N1)pdm09 clade 6B.1A.5a.2a. Vaccinated individuals benefited from the A/Victoria/2570/2019 (H1N1)pdm09-like antigen, which conferred good protection against medically attended CLI. If similar viruses predominate in the northern hemisphere, our estimates of 2023 southern hemisphere influenza VE suggest that 2023&#x02013;24 northern hemisphere influenza vaccines, which include similar H1N1 antigens, could provide similar protection during the upcoming northern hemisphere influenza season.</p><sec sec-type="supplementary-material" id="SM1"><title>Supplementary Material</title><supplementary-material id="SD1" position="float" content-type="local-data"><label>Supplemental 2</label><media xlink:href="NIHMS1986353-supplement-Supplemental_2.pdf" id="d66e248" position="anchor"/></supplementary-material><supplementary-material id="SD2" position="float" content-type="local-data"><label>Supplemental 1</label><media xlink:href="NIHMS1986353-supplement-Supplemental_1.pdf" id="d66e251" position="anchor"/></supplementary-material></sec></body><back><ack id="S1"><p id="P12">JGAR has received support from the US CDC. CZ has received support from the US CDC and Pfizer as an international expert for an expert&#x02019;s symposia. FK has received support from the US CDC, grants or contracts from the Belgian Directorate of Development Cooperation, the Fogarty International Center of the US NIH, Pfizer as an international expert for an expert&#x02019;s symposia, Abbott as a key opinion leader advisory board member, and Peruvian Multisectoral Committee to combat antimicrobial resistance as an unpaid member. VGSRC has received support from the US CDC. EGL has received support from the US CDC, the Fogarty International Center of the US NIH, the University of Alabama at Birmingham for the Gorgas Advanced Course, Pfizer as an international expert to support an expert&#x02019;s symposia, the Peruvian Ministry of Health as an unpaid expert, and CFAR at the University of Washington Seattle as an unpaid member. All other authors declare no competing interests. This study was supported by the US Centers for Disease Control and Prevention cooperative agreement award GH00266. CZ and EG had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. FK, JGAR, CZ, VGSRC, FM, PT, EGL, and EG conceived and designed the study. EM coordinated laboratory analysis. PT performed genomic sequencing. PA, FG, SA, CM, VN, MG, and RC coordinated data collection and management. CSNV, DB, and VGSRC performed the statistical analysis. All authors wrote and approved the final manuscript. NK, FK, and EGL drafted, edited, and reviewed the manuscript. LC, AF, and EAB interpreted the findings and edited the manuscript. Data will be shared by the corresponding author upon reasonable request for research purposes. We recognise the contributions from several individuals and institutions to this project, including those from Dr Jorge Ponce, Dr Irma Hidalgo, and Mg Luz Nateros (Diris Lima Centro); Dr Roger Hern&#x000e1;ndez and Dr Ana Quintana (Hospital Cayetano Heredia); Dr C&#x000e9;sar Munayco (CDC Peru); Dr Anna Chard and Dr Sof&#x000ed;a Arriola (CDC); and Dr Steev Loyola (Universidad Peruana Cayetano Heredia). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention.</p></ack><ref-list><ref id="R1"><label>1</label><mixed-citation publication-type="journal"><name><surname>Chard</surname><given-names>AN</given-names></name>, <name><surname>Nogareda</surname><given-names>F</given-names></name>, <name><surname>Regan</surname><given-names>AK</given-names></name>, <etal/>
<article-title>End-of-season influenza vaccine effectiveness during the southern hemisphere 2022 influenza season - Chile, Paraguay, and Uruguay</article-title>. <source>Int J Infect Dis</source>
<year>2023</year>; <volume>134</volume>: <fpage>39</fpage>&#x02013;<lpage>44</lpage>.<pub-id pub-id-type="pmid">37201863</pub-id>
</mixed-citation></ref><ref id="R2"><label>2</label><mixed-citation publication-type="journal"><name><surname>Barraza</surname><given-names>MF</given-names></name>, <name><surname>Fasce</surname><given-names>RA</given-names></name>, <name><surname>Nogareda</surname><given-names>F</given-names></name>, <etal/>
<article-title>Influenza incidence and vaccine effectiveness during the southern hemisphere influenza season - Chile, 2022</article-title>. <source>MMWR Morb Mortal Wkly Rep</source>
<year>2022</year>; <volume>71</volume>: <fpage>1353</fpage>&#x02013;<lpage>58</lpage>.<pub-id pub-id-type="pmid">36301733</pub-id>
</mixed-citation></ref><ref id="R3"><label>3</label><mixed-citation publication-type="journal"><collab>Centers for Disease Control and Prevention</collab>. <source>Coronavirus disease 2019 (COVID-19) 2021 case definition</source>. <year>2021</year>. <comment><ext-link xlink:href="https://ndc.services.cdc.gov/case-definitions/coronavirus-disease-2019-2021/" ext-link-type="uri">https://ndc.services.cdc.gov/case-definitions/coronavirus-disease-2019-2021/</ext-link></comment> (<date-in-citation>accessed Aug 25, 2023</date-in-citation>).</mixed-citation></ref><ref id="R4"><label>4</label><mixed-citation publication-type="journal"><name><surname>Nagy</surname><given-names>A</given-names></name>, <name><surname>&#x0010c;ern&#x000ed;kov&#x000e1;</surname><given-names>L</given-names></name>, <name><surname>Kunteov&#x000e1;</surname><given-names>K</given-names></name>, <etal/>
<article-title>A universal RT-qPCR assay for &#x0201c;One Health&#x0201d; detection of influenza A viruses</article-title>. <source>PloS One</source>
<year>2021</year>; <volume>16</volume>: <fpage>e0244669</fpage>.<pub-id pub-id-type="pmid">33471840</pub-id>
</mixed-citation></ref><ref id="R5"><label>5</label><mixed-citation publication-type="journal"><name><surname>Sahajpal</surname><given-names>NS</given-names></name>, <name><surname>Mondal</surname><given-names>AK</given-names></name>, <name><surname>Njau</surname><given-names>A</given-names></name>, <etal/>
<article-title>High-throughput next-generation sequencing respiratory viral panel: a diagnostic and epidemiologic tool for SARS-CoV-2 and other viruses</article-title>. <source>Viruses</source>
<year>2021</year>; <volume>13</volume>: <fpage>2063</fpage>.<pub-id pub-id-type="pmid">34696495</pub-id>
</mixed-citation></ref><ref id="R6"><label>6</label><mixed-citation publication-type="journal"><name><surname>Jackson</surname><given-names>ML</given-names></name>, <name><surname>Nelson</surname><given-names>JC</given-names></name>. <article-title>The test-negative design for estimating influenza vaccine effectiveness</article-title>. <source>Vaccine</source>
<year>2013</year>; <volume>31</volume>: <fpage>2165</fpage>&#x02013;<lpage>68</lpage>.<pub-id pub-id-type="pmid">23499601</pub-id>
</mixed-citation></ref><ref id="R7"><label>7</label><mixed-citation publication-type="journal"><name><surname>Tinoco</surname><given-names>YO</given-names></name>, <name><surname>Azziz-Baumgartner</surname><given-names>E</given-names></name>, <name><surname>Uyeki</surname><given-names>TM</given-names></name>, <etal/>
<article-title>Burden of influenza in 4 ecologically distinct regions of Peru: household active surveillance of a community cohort, 2009&#x02013;2015</article-title>. <source>Clin Infect Dis</source>
<year>2017</year>; <volume>65</volume>: <fpage>1532</fpage>&#x02013;<lpage>41</lpage>.<pub-id pub-id-type="pmid">29020267</pub-id>
</mixed-citation></ref><ref id="R8"><label>8</label><mixed-citation publication-type="journal"><name><surname>Fowlkes</surname><given-names>AL</given-names></name>, <name><surname>Nogareda</surname><given-names>F</given-names></name>, <name><surname>Regan</surname><given-names>A</given-names></name>, <etal/>
<article-title>Interim effectiveness estimates of 2023 southern hemisphere influenza vaccines in preventing influenza-associated hospitalizations - REVELAC-i network, March&#x02013;July 2023</article-title>. <source>MMWR Morb Mortal Wkly Rep</source>
<year>2023</year>; <volume>72</volume>: <fpage>1010</fpage>&#x02013;<lpage>15</lpage>.<pub-id pub-id-type="pmid">37708084</pub-id>
</mixed-citation></ref></ref-list></back></article>