{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:58Z","timestamp":1792790398018,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,16]]},"group-title":"Epidemiology","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases","award":["R01 AI099631"],"award-info":[{"award-number":["R01 AI099631"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["P01 AI106695"],"award-info":[{"award-number":["P01 AI106695"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["U19 AI118610"],"award-info":[{"award-number":["U19 AI118610"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Chikungunya (CHIKV) and Zika (ZIKV) viruses have caused widespread epidemics across the Americas. After several years of minimal transmission, CHIKV is once again spreading in Nicaragua. We investigated spatial aspects of two chikungunya epidemics (2014, 2015) and one Zika epidemic (2016) in a prospective pediatric cohort in Nicaragua. We used generalized estimating equations, generalized additive and mixed-effects models, Kuldorff\u2019s scan statistic, and intracluster correlations to analyze the infection and disease status of \u223c3,000 initially uninfected participants during each epidemic. We found that the incidence of infection (# new infections\/total population) and disease (# new cases\/total population) often had different spatial patterns, demonstrating that high-infection areas may not exhibit much disease. High infection incidence was observed near a large cemetery west of the study site. The large 2015 chikungunya epidemic and 2016 Zika epidemic started near the cemetery, exhibited high infection incidence throughout the study site, and had extensive month-to-month changes in spatiotemporal dynamics. Clusters of excess infections were large and adjacent to the cemetery, while clusters of excess uninfected participants were found in the northern and eastern sections of the study area. Notably, the intracluster correlation of infection was very weak in households (\u223c0.2), and infection status was correlated across distances &lt;200 meters. Similarities across the epidemics suggest that targeting interventions to the built, non-household environment may reduce epidemic potential in Managua. Overall, spatial analyses of epidemics that only use case data may substantially underestimate the full extent of viral transmission, missing identification of high-infection areas and opportunities for intervention.<\/jats:p>","DOI":"10.64898\/2026.09.15.26363072","type":"posted-content","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:45:19Z","timestamp":1789609519000},"source":"Crossref","is-referenced-by-count":0,"title":["Spatial analyses of infection and disease during chikungunya and Zika epidemics in Managua, Nicaragua"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7263-5625","authenticated-orcid":false,"given":"Fausto Andres","family":"Bustos Carrillo","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, 94720-3370"},{"name":"Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, California, 94720-7360"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Lopez Mercado","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, 14006, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jairo","family":"Carey Monterrey","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, 14006, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0878-3260","authenticated-orcid":false,"given":"Damaris","family":"Collado","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, 14006, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Miranda","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, 14006, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saira","family":"Saborio","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, 14006, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Ojeda","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, 14006, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0070-3895","authenticated-orcid":false,"given":"Nery","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, 14006, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Plazaola","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, 14006, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0383-6896","authenticated-orcid":false,"given":"Harold","family":"Suazo Laguna","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, 14006, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0915-5273","authenticated-orcid":false,"given":"Sonia","family":"Arguello","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, 14006, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0029-3101","authenticated-orcid":false,"given":"Hugh","family":"Sturrock","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, San Francisco, California, 94158"},{"name":"Locational, Poole, Dorset, BH16 6FA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3812-5978","authenticated-orcid":false,"given":"Angel","family":"Balmaseda","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, 14006, Nicaragua"},{"name":"Laboratorio Nacional de Virolog\u00eda, Centro Nacional de Diagn\u00f3stico y Referencia, Ministerio de Salud, Managua, 16064, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-173X","authenticated-orcid":false,"given":"Guillermina","family":"Kuan","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, 14006, Nicaragua"},{"name":"Centro de Salud S\u00f3crates Flores Vivas, Ministerio de Salud, Managua, 12005, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7238-4037","authenticated-orcid":false,"given":"Eva","family":"Harris","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, 94720-3370"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091911201063000_2026.09.15.26363072v1.1","unstructured":"Higgs S , Vanlandingham D , Powers A , editors. Chikungunya and Zika Viruses: Global Emerging Health Threats. 1st ed. Academic Press; 2018."},{"key":"2026091911201063000_2026.09.15.26363072v1.2","unstructured":"Pan American Health Organization. Regional Health Data in the Americas. 2026."},{"issue":"9","key":"2026091911201063000_2026.09.15.26363072v1.3","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S2352-4642(25)00168-3","article-title":"Comparison of dengue, chikungunya, and Zika among children in Nicaragua across 18 years: a single-centre, prospective cohort study","volume":"9","year":"2025","journal-title":"Lancet Child Adolesc Heal"},{"issue":"3","key":"2026091911201063000_2026.09.15.26363072v1.4","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S1473-3099(19)30547-X","article-title":"Age-dependent manifestations and case definitions of paediatric Zika: a prospective cohort study","volume":"20","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"2026091911201063000_2026.09.15.26363072v1.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004042"},{"key":"2026091911201063000_2026.09.15.26363072v1.6","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2003.69.494"},{"key":"2026091911201063000_2026.09.15.26363072v1.7","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1602024"},{"key":"2026091911201063000_2026.09.15.26363072v1.8","doi-asserted-by":"crossref","unstructured":"Sun H , Binder RA , Dickens B , de Sessions PF , Rabaa MA , Ho EXP , et al. Viral genome- based Zika virus transmission dynamics in a paediatric cohort during the 2016 Nicaragua epidemic. EBioMedicine. 2021 Oct 1;72.","DOI":"10.1016\/j.ebiom.2021.103596"},{"key":"2026091911201063000_2026.09.15.26363072v1.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1611391113"},{"key":"2026091911201063000_2026.09.15.26363072v1.10","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.17.201541"},{"issue":"4","key":"2026091911201063000_2026.09.15.26363072v1.11","first-page":"e01622","article-title":"Epidemiological evidence for lineage-specific differences in the risk of inapparent chikungunya virus infection","volume":"93","year":"2019","journal-title":"J Virol"},{"issue":"37","key":"2026091911201063000_2026.09.15.26363072v1.12","doi-asserted-by":"crossref","first-page":"9294","DOI":"10.1073\/pnas.1804672115","article-title":"Seroprevalence, risk factor, and spatial analyses of Zika virus infection after the 2016 epidemic in Managua","volume":"115","year":"2018","journal-title":"Nicaragua. Proc Natl Acad Sci"},{"key":"2026091911201063000_2026.09.15.26363072v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwp092"},{"key":"2026091911201063000_2026.09.15.26363072v1.14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004773"},{"key":"2026091911201063000_2026.09.15.26363072v1.15","doi-asserted-by":"publisher","DOI":"10.1086\/648592"},{"key":"2026091911201063000_2026.09.15.26363072v1.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1704984114"},{"key":"2026091911201063000_2026.09.15.26363072v1.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1704984114"},{"key":"2026091911201063000_2026.09.15.26363072v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2016.01.007"},{"key":"2026091911201063000_2026.09.15.26363072v1.19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002726"},{"key":"2026091911201063000_2026.09.15.26363072v1.20","unstructured":"World Health Organization. Dengue haemorrhagic fever: Diagnosis, treatment, prevention, and control, 2nd ed. Geneva; 1997."},{"key":"2026091911201063000_2026.09.15.26363072v1.21","unstructured":"World Health Organization - Regional Office for South-East Asia. Guidelines for prevention and control of Chikungunya fever. 2009. p. 19."},{"key":"2026091911201063000_2026.09.15.26363072v1.22","unstructured":"ProMED. Doen\u00e7a misteriosa assusta popula\u00e7\u00e3o de Cama\u00e7ari. 2015."},{"key":"2026091911201063000_2026.09.15.26363072v1.23","unstructured":"Hastie T , Tibshirani R . Generalized Additive Models. New York: Chapman & Hall; 1990."},{"issue":"6","key":"2026091911201063000_2026.09.15.26363072v1.24","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1080\/03610929708831995","article-title":"A spatial scan statistic","volume":"26","year":"1997","journal-title":"Commun Stat - Theory Methods"},{"issue":"1","key":"2026091911201063000_2026.09.15.26363072v1.25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12942-016-0056-6","article-title":"Using Gini coefficient to determining optimal cluster reporting sizes for spatial scan statistics","volume":"15","year":"2016","journal-title":"Int J Health Geogr"},{"issue":"8","key":"2026091911201063000_2026.09.15.26363072v1.26","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1111\/ecog.00566","article-title":"Testing environmental and genetic effects in the presence of spatial autocorrelation","volume":"37","year":"2014","journal-title":"Ecography (Cop"},{"issue":"2","key":"2026091911201063000_2026.09.15.26363072v1.27","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1365-3156.2006.01781.x","article-title":"Review: Artificial container-breeding mosquitoes and cemeteries: A perfect match","volume":"12","year":"2007","journal-title":"Trop Med Int Heal"},{"key":"2026091911201063000_2026.09.15.26363072v1.28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120621109"},{"key":"2026091911201063000_2026.09.15.26363072v1.29","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2019.1867"},{"key":"2026091911201063000_2026.09.15.26363072v1.30","doi-asserted-by":"crossref","unstructured":"Bisanzio D , Dzul-Manzanilla F , Gomez-Dant\u00e9s H , Pavia-Ruz N , Hladish TJ , Lenhart A , et al. Spatio-temporal coherence of dengue, chikungunya and Zika outbreaks in Merida, Mexico. PLoS Negl Trop Dis. 2018 Mar 15;12(3).","DOI":"10.1371\/journal.pntd.0006298"},{"issue":"8","key":"2026091911201063000_2026.09.15.26363072v1.31","first-page":"e0003977","volume":"9","year":"2015","journal-title":"Spatial and Temporal Clustering of Chikungunya Virus Transmission in Dominica"},{"key":"2026091911201063000_2026.09.15.26363072v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2018.04.023"},{"issue":"10","key":"2026091911201063000_2026.09.15.26363072v1.33","doi-asserted-by":"crossref","first-page":"e0008760","DOI":"10.1371\/journal.pntd.0008760","article-title":"Spatiotemporal transmission dynamics of co-circulating dengue, Zika, and chikungunya viruses in Fortaleza, Brazil: 2011\u20132017","volume":"14","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"key":"2026091911201063000_2026.09.15.26363072v1.34","first-page":"e62","article-title":"Spatial analysis of probable cases of dengue fever, chikungunya fever and zika virus infections in Maranhao State, Brazil","volume":"60","year":"2018","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"2026091911201063000_2026.09.15.26363072v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2018.02.007"},{"key":"2026091911201063000_2026.09.15.26363072v1.36","doi-asserted-by":"crossref","unstructured":"McHale T , Romero-Vivas C , Fronterre C , Arango-Padilla P , Waterlow N , Nix C , et al. Spatiotemporal heterogeneity in the distribution of chikungunya and Zika virus case incidences during their 2014 to 2016 epidemics in Barranquilla, Colombia. Int J Environ Res Public Health. 2019 May 2;16(10).","DOI":"10.3390\/ijerph16101759"},{"key":"2026091911201063000_2026.09.15.26363072v1.37","doi-asserted-by":"crossref","unstructured":"Zambrano LI , Vasquez-Bonilla WO , Fuentes-Barahona IC , Cl\u00e1udio da Silva J , Valle- Reconco JA , Medina MT , et al. Spatial distribution of Zika in Honduras during 2016\u2013 2017 using geographic information systems (GIS) \u2013 Implications for public health and travel medicine. Travel Med Infect Dis. 2019 Sep 1;31.","DOI":"10.1016\/j.tmaid.2019.01.017"},{"key":"2026091911201063000_2026.09.15.26363072v1.38","doi-asserted-by":"crossref","unstructured":"Chien LC , Lin RT , Liao Y , Sy FS , P\u00e9rez A . Surveillance on the endemic of Zika virus infection by meteorological factors in Colombia: A population-based spatial and temporal study. BMC Infect Dis. 2018 Apr 17;18(1).","DOI":"10.1186\/s12879-018-3085-x"},{"key":"2026091911201063000_2026.09.15.26363072v1.39","doi-asserted-by":"crossref","unstructured":"Bonilla-Aldana DK , Bonilla-Aldana JL , Garc\u00eda-Bustos JJ , Lozada CO , Rodr\u00edguez- Morales AJ . Geographical trends of chikungunya and Zika in the Colombian Amazonian gateway department, Caqueta, 2015\u20132018 \u2013 Implications for public health and travel medicine. Travel Med Infect Dis. 2020 May 1;35.","DOI":"10.1016\/j.tmaid.2019.101481"},{"key":"2026091911201063000_2026.09.15.26363072v1.40","doi-asserted-by":"crossref","unstructured":"Vissoci JRN , Rocha TAH , Silva NC da , de Sousa Queiroz RC , Thomaz EBAF , Amaral PVM , et al. Zika virus infection and microcephaly: Evidence regarding geospatial associations. PLoS Negl Trop Dis. 2018 Apr 25;12(4).","DOI":"10.1371\/journal.pntd.0006392"},{"key":"2026091911201063000_2026.09.15.26363072v1.41","doi-asserted-by":"crossref","unstructured":"Dalvi APR , Braga JU . Spatial diffusion of the 2015\u20132016 Zika, dengue and chikungunya epidemics in Rio de Janeiro Municipality, Brazil. Epidemiol Infect. 2019;147.","DOI":"10.1017\/S0950268819001250"},{"key":"2026091911201063000_2026.09.15.26363072v1.42","doi-asserted-by":"crossref","unstructured":"Santana LS , Braga JU . Spatial diffusion of zika fever epidemics in the municipality Salvador-Bahia, Brazil, in 2015-2016: Does Zika fever have the same spread pattern as Dengue and Chikungunya fever epidemics? Rev Soc Bras Med Trop. 2020;53.","DOI":"10.1590\/0037-8682-0563-2019"},{"key":"2026091911201063000_2026.09.15.26363072v1.43","doi-asserted-by":"publisher","DOI":"10.1086\/222356"},{"key":"2026091911201063000_2026.09.15.26363072v1.44","unstructured":"Openshaw S , Taylor P . A million or so correlation coefficients: three experiments on the modifiable areal unit problem. In: Wrigley N, editor. Statistical applications in the spatial sciences. London, UK: Pion; 1979. p. 127\u201344."},{"key":"2026091911201063000_2026.09.15.26363072v1.45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007213"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.15.26363072","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:20:24Z","timestamp":1789842024000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.09.15.26363072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":45,"URL":"https:\/\/doi.org\/10.64898\/2026.09.15.26363072","relation":{},"subject":[],"published":{"date-parts":[[2026,9,16]]},"subtype":"preprint"}}