Zika virus disease, microcephaly and Guillain-Barré syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017

Background: The Zika virus disease (ZVD) has had a huge impact on public health in Colombia for the numbers of people affected and the presentation of Guillain-Barre syndrome (GBS) and microcephaly cases associated to ZVD. Methods: A retrospective descriptive study was carried out, we analyze the ep...

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Autores:
Méndez Álvarez, Nelson David
Oviedo Pastrana, Misael Enrique
Mattar Velilla, Ameth Salim
Caicedo Castro, Isaac
Arrieta Bernate, Germán Javier
Tipo de recurso:
Article of investigation
Fecha de publicación:
2017
Institución:
Corporación Universitaria del Caribe - CECAR
Repositorio:
Repositorio Digital CECAR
Idioma:
eng
OAI Identifier:
oai:repositorio.cecar.edu.co:cecar/10894
Acceso en línea:
https://repositorio.cecar.edu.co/handle/cecar/10894
Palabra clave:
Infectious diseases vectors
Epidemiology
Culicidae
Morbidity
Nervous system congenital abnormalities
Education
Public health professional
Population
Rights
openAccess
License
Derechos reservados - Corporación Universitaria de Caribe - CECAR
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oai_identifier_str oai:repositorio.cecar.edu.co:cecar/10894
network_acronym_str RepoCECAR2
network_name_str Repositorio Digital CECAR
repository_id_str
dc.title.eng.fl_str_mv Zika virus disease, microcephaly and Guillain-Barré syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017
title Zika virus disease, microcephaly and Guillain-Barré syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017
spellingShingle Zika virus disease, microcephaly and Guillain-Barré syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017
Infectious diseases vectors
Epidemiology
Culicidae
Morbidity
Nervous system congenital abnormalities
Education
Public health professional
Population
title_short Zika virus disease, microcephaly and Guillain-Barré syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017
title_full Zika virus disease, microcephaly and Guillain-Barré syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017
title_fullStr Zika virus disease, microcephaly and Guillain-Barré syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017
title_full_unstemmed Zika virus disease, microcephaly and Guillain-Barré syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017
title_sort Zika virus disease, microcephaly and Guillain-Barré syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017
dc.creator.fl_str_mv Méndez Álvarez, Nelson David
Oviedo Pastrana, Misael Enrique
Mattar Velilla, Ameth Salim
Caicedo Castro, Isaac
Arrieta Bernate, Germán Javier
dc.contributor.author.none.fl_str_mv Méndez Álvarez, Nelson David
Oviedo Pastrana, Misael Enrique
Mattar Velilla, Ameth Salim
Caicedo Castro, Isaac
Arrieta Bernate, Germán Javier
dc.contributor.corporatename.none.fl_str_mv Corporación Universitaria del caribe - CECAR
dc.contributor.researchgroup.none.fl_str_mv Salud Pública y Auditoría en Salud
dc.subject.proposal.none.fl_str_mv Infectious diseases vectors
Epidemiology
Culicidae
Morbidity
Nervous system congenital abnormalities
Education
Public health professional
Population
topic Infectious diseases vectors
Epidemiology
Culicidae
Morbidity
Nervous system congenital abnormalities
Education
Public health professional
Population
description Background: The Zika virus disease (ZVD) has had a huge impact on public health in Colombia for the numbers of people affected and the presentation of Guillain-Barre syndrome (GBS) and microcephaly cases associated to ZVD. Methods: A retrospective descriptive study was carried out, we analyze the epidemiological situation of ZVD and its association with microcephaly and GBS during a 21-month period, from October 2015 to June 2017. The variables studied were: (i) ZVD cases, (ii) ZVD cases in pregnant women, (iii) laboratory-confirmed ZVD in pregnant women, (iv) ZVD cases associated with microcephaly, (v) laboratory-confirmed ZVD associated with microcephaly, and (vi) ZVD associated to GBS cases. Average number of cases, attack rates (AR) and proportions were also calculated. The studied variables were plotted by epidemiological weeks and months. The distribution of ZVD cases in Colombia was mapped across the time using Kernel density estimator and QGIS software; we adopted Kernel Ridge Regression (KRR) and the Gaussian Kernel to estimate the number of Guillain Barre cases given the number of ZVD cases. Results: One hundred eight thousand eighty-seven ZVD cases had been reported in Colombia, including 19,963 (18. 5%) in pregnant women, 710 (0.66%) associated with microcephaly (AR, 4.87 cases per 10,000 live births) and 453 (0. 42%) ZVD associated to GBS cases (AR, 41.9 GBS cases per 10,000 ZVD cases). It appears the cases of GBS increased in parallel with the cases of ZVD, cases of microcephaly appeared 5 months after recognition of the outbreak. The kernel density map shows that throughout the study period, the states most affected by the Zika outbreak in Colombia were mainly San Andrés and Providencia islands, Casanare, Norte de Santander, Arauca and Huila. The KRR shows that there is no proportional relationship between the number of GBS and ZVD cases. During the cross validation, the RMSE achieved for the second order polynomial kernel, the linear kernel, the sigmoid kernel, and the Gaussian kernel are 9.15, 9.2, 10.7, and 7.2 respectively. Conclusions: This study updates the epidemiological analysis of the ZVD situation in Colombia describes the geographical distribution of ZVD and shows the functional relationship between ZVD cases and GBS.
publishDate 2017
dc.date.issued.none.fl_str_mv 2017
dc.date.accessioned.none.fl_str_mv 2025-09-08T15:40:11Z
dc.type.none.fl_str_mv Artículo de revista
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dc.identifier.eissn.none.fl_str_mv 2049-3258
url https://repositorio.cecar.edu.co/handle/cecar/10894
identifier_str_mv 2049-3258
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language eng
dc.relation.citationendpage.none.fl_str_mv 11
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dc.relation.citationvolume.none.fl_str_mv Volumen 76
dc.relation.ispartofjournal.none.fl_str_mv Archives of Public Health
dc.relation.references.none.fl_str_mv Mattar S, Tique V, Miranda J, Montes JE, Garzon D. Undifferentiated tropical febrile illness in Córdoba, Colombia Not everything is dengue. J Infect Public Health. 2017;10:507–12. http://dx.doi.org/10.1016/j.jiph.2016.09.014.
Mattar S, Ojeda C, Arboleda J, Arrieta G, Bosch I, Botia I, et al. Case report: microcephaly associated with Zika virus infection. Colombia BMC Infectious Diseases. 2017;17:423. https://doi.org/10.1186/s12879-017-2522-6.
Pan American Health Organization / World Health Organization. Regional Zika Epidemiological Update (Americas) March 10, 2017. Washington, D.C. D.C. 20037, United States of America. 2017. http://www2.paho.org/hq/index. php?option=com_content&view=article&id=11599&Itemid=41691&lang=en. Accessed 23 Apr 2017.
Pan American Health Organization / World Health Organization. Zika suspected and confirmed cases reported by countries and territories in the Americas Cumulative cases, 2015–2017. Updated as of 20 April 2017. Washington, D.C.: 2017. http://www2.paho.org/hq/index.php?option=com_ docman&task=doc_view&Itemid=270&gid=39552&lang=es.
Instituto Nacional de Salud (Colombia). Boletin Epidemiologico Semanal. Semana epidemiológica número 40 de 2015. Bogota D.C. 2017. http://www.ins.gov.co/ boletin-epidemiologico/Boletn%20Epidemiolgico/2015%20Boletin% 20epidemiologico%20semana%2040.pdf. Accessed 3 Mar 2017.
Instituto Nacional de Salud (Colombia). Semana epidemiológica número 52 de 2016. Bogotá, D.C.: 2017. http://www.ins.gov.co/boletin-epidemiologico/ Boletn%20Epidemiolgico/2016%20Bolet%C3%ADn%20epidemiol%C3% B3gico%20semana%2052%20-.pdf. Accessed 17 Feb 2017.
Pacheco O, Beltrán M, Nelson CA, Valencia D, Tolosa N, Farr SL, Padilla AV, Tong VT, Cuevas EL, Espinosa-Bode A, et al. Zika virus disease in Colombia — preliminary report. N Engl J Med. 2016. doi: 10.1056/NEJMoa1604037.
Parra B, Lizarazo J, Jiménez-Arango JA, Zea-Vera AF, González-Manrique G, Vargas J, Angarita JA, Zuñiga G, Lopez-Gonzalez R, Beltran CL, et al. Guillain–Barré syndrome associated with Zika virus infection in Colombia. N Engl J Med. 2016;375:1513–23.
Cuevas EL, Tong VT, Rozo N, Valencia D, Pacheco O, Gilboa SM, et al. Preliminary report of microcephaly potentially associated with Zika virus infection during pregnancy — Colombia, January–November 2016. MMWR Morb Mortal Wkly Rep. 2016;65:1409–13.
Camacho E, Paternina-Gomez M, Blanco PJ, Osorio JE, Aliota MT. Detection of autochthonous Zika virus transmission in Sincelejo, Colombia. Emerg Infect Dis. 2016;22:927–9.
Rojas DP, Dean NE, Yang Y, Kenah E, Quintero J, Tomasi S, Ramirez EL, Kelly Y, Castro C, Carrasquilla G, et al. The epidemiology and transmissibility of Zika virus in Girardot and San Andres island, Colombia, September 2015 to January 2016. Euro Surveill. 2016;21. http://dx.doi.org/10.2807/1560-7917.ES.2016.21.28.30283.
Towers S, Brauer F, Castillo-Chavez C, Falconar AK, Mubayi A, Romero-Vivas CM. Estimate of the reproduction number of the 2015 Zika virus outbreak in Barranquilla, Colombia, and estimation of the relative role of sexual transmission. Epidemics. 2016;17:50–5.
Instituto Nacional de Salud (Colombia). Boletín Epidemiológico. Bogotá, D. C.: 2017. http://www.ins.gov.co/boletin-epidemiologico/Paginas/default.aspx. Accessed 12 Feb 2017.
Ministerio de Salud y Protección Social - Instituto Nacional de Salud (Colombia). Circular conjunta externa N° 00000061 de 2015. Vigilancia de la fiebre por virus Zika (ZIKV) en su fase II epidémica y fortalecimiento de la prevencion de la fiebre por virus Zika en grupos de riesgo. Bogotá, D.C.: 2017. http://www.ins.gov.co/Noticias/ZIKA/Circular%20Conj%20061%202015%20 Fiebre%20zika.pdf. Accessed 12 Feb 2017.
Ministerio de Salud y Protección Social - Instituto Nacional de Salud (Colombia). Protocolo de vigilancia en salud pública: enfermedad por virus Zika. Bogotá, D.C; 2017. http://bvs.minsa.gob.pe/local/MINSA/3449.pdf. Accesed 14 Jul 2017
Departamento Administrativo Nacional de Estadística (DANE, Colombia). Catálogo de Objetos Geográficos del Marco Geoestadístico Nacional. Dirección de Geoestadística, 2014. Bogotá, D.C.: 2017. http://www.dane.gov.co/. Accessed 19 Sept 2017.
Departamento Administrativo Nacional de Estadística (DANE, Colombia). Estadísticas vitales nacimientos y defunciones. Bogotá, D.C.: 2017. https:// www.dane.gov.co/index.php/estadisticas-por-tema/demografia-y-poblacion/ nacimientos-y-defunciones. Accessed 18 Sept 2017.
Departamento Administrativo Nacional de Estadística (DANE, Colombia). Catálogo de Objetos Geográficos del Marco Geoestadístico Nacional. Dirección de Geoestadística, 2014. Bogotá, D.C.: 2017. http://www.dane.gov.co/. Accessed 18 Sept 2017.
Kloog I, Haim A, Portnov BA. Using kernel density function as an urban analysis tool: investigating the association between nightlight exposure and the incidence of breast cancer in Haifa, Israel. Comput Environ Urban Syst. 2009;33:55–63.
Saunders C, Gammerman A, Vovk V. Ridge regression learning algorithm in dual variables. En (ICML-1998) Proceedings of the 15th International Conference on Machine Learning. Morgan Kaufmann. 1998:515–21.
Pan American Health Organization / World Health Organization. Zika suspected and confirmed cases reported by countries and territories in the Americas Cumulative cases, 2015–2017. Updated as of 13 July 2017. Washington, D.C.: 2017. http://www.paho.org/hq/index.php?option=com_docman&task=doc_ view&Itemid=270&gid=40858&lang=es. Accessed 14 Jul 2017.
Rojas DP, Dean NE, Yang Y, Kenah E, Quintero J, Tomasi S, et al. The epidemiology and transmissibility of Zika virus in Girardot and San Andres island, Colombia, September 2015 to January 2016. Euro Surveill. 2016;21(28). doi: 10.2807/1560-7917.ES.2016.21.28.30283.
Jimenez Corona ME, De la Garza Barroso AL, Rodriguez Martínez JC, et al. Clinical and Epidemiological Characterization of Laboratory-Confirmed Autochthonous Cases of Zika Virus Disease in Mexico. PLoS Currents. 2016;8:ecurrents.outbreaks.a2fe1b3d6d71e24ad2b5afe982824053. doi:https:// doi.org/10.1371/currents.outbreaks.a2fe1b3d6d71e24ad2b5afe982824053.
Oviedo-Pastrana M, Méndez N, Mattar S, Arrieta G, Gomezcaceres L. Epidemic outbreak of chikungunya in two neighboring towns in the Colombian Caribbean: a survival analysis. Archives of Public Health. 2017;75:1. doi: 10.1186/s13690-016-0169-1.
Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika virus and birth defects — reviewing the evidence for causality. N Engl J Med. 2016;374:1981–7.
Ministerio de Salud y Protección Social (Colombia). Lineamientos para la detección y manejo clínico integral de anomalías congénitas en fetos expuestos al virus del Zika durante la gestación de pacientes en Colombia. Bogotá, D.C.: 2017. https://www.minsalud.gov.co/sites/rid/Lists/ BibliotecaDigital/RIDE/VS/PP/ET/linea-deteccion-manejo-clinico-anomaliacongenitas-fotos-zika.pdf. Accessed 3 Mar 2017.
Center for Disease Control and Prevention. CDC and the Instituto Nacional de Salud of Colombia collaborate to understand long-term effects of Zika virus infection during pregnancy. Atlanta.: 2017. https://www.cdc.gov/media/releases/ 2016/p0902-cdc-colombia-collaboration.html. Accessed 18 Sept 2017.
Center for Disease Control and Prevention. Microcephaly & Other Birth Defects. Atlanta.: 2017. https://www.cdc.gov/zika/healtheffects/birth_defects.html. Accessed 18 Sept 2017.
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spelling Méndez Álvarez, Nelson DavidOviedo Pastrana, Misael EnriqueMattar Velilla, Ameth SalimCaicedo Castro, IsaacArrieta Bernate, Germán JavierCorporación Universitaria del caribe - CECARSalud Pública y Auditoría en Salud2025-09-08T15:40:11Z2017https://repositorio.cecar.edu.co/handle/cecar/108942049-3258Background: The Zika virus disease (ZVD) has had a huge impact on public health in Colombia for the numbers of people affected and the presentation of Guillain-Barre syndrome (GBS) and microcephaly cases associated to ZVD. Methods: A retrospective descriptive study was carried out, we analyze the epidemiological situation of ZVD and its association with microcephaly and GBS during a 21-month period, from October 2015 to June 2017. The variables studied were: (i) ZVD cases, (ii) ZVD cases in pregnant women, (iii) laboratory-confirmed ZVD in pregnant women, (iv) ZVD cases associated with microcephaly, (v) laboratory-confirmed ZVD associated with microcephaly, and (vi) ZVD associated to GBS cases. Average number of cases, attack rates (AR) and proportions were also calculated. The studied variables were plotted by epidemiological weeks and months. The distribution of ZVD cases in Colombia was mapped across the time using Kernel density estimator and QGIS software; we adopted Kernel Ridge Regression (KRR) and the Gaussian Kernel to estimate the number of Guillain Barre cases given the number of ZVD cases. Results: One hundred eight thousand eighty-seven ZVD cases had been reported in Colombia, including 19,963 (18. 5%) in pregnant women, 710 (0.66%) associated with microcephaly (AR, 4.87 cases per 10,000 live births) and 453 (0. 42%) ZVD associated to GBS cases (AR, 41.9 GBS cases per 10,000 ZVD cases). It appears the cases of GBS increased in parallel with the cases of ZVD, cases of microcephaly appeared 5 months after recognition of the outbreak. The kernel density map shows that throughout the study period, the states most affected by the Zika outbreak in Colombia were mainly San Andrés and Providencia islands, Casanare, Norte de Santander, Arauca and Huila. The KRR shows that there is no proportional relationship between the number of GBS and ZVD cases. During the cross validation, the RMSE achieved for the second order polynomial kernel, the linear kernel, the sigmoid kernel, and the Gaussian kernel are 9.15, 9.2, 10.7, and 7.2 respectively. Conclusions: This study updates the epidemiological analysis of the ZVD situation in Colombia describes the geographical distribution of ZVD and shows the functional relationship between ZVD cases and GBS.Auditoría en SaludSalud Pública11 páginasapplication/pdfengDerechos reservados - Corporación Universitaria de Caribe - CECARhttps://creativecommons.org/licenses/by-nc/4.0/Atribución-NoComercial 4.0 Internacional (CC BY-NC 4.0)info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2DOI 10.1186/s13690-017-0233-5Zika virus disease, microcephaly and Guillain-Barré syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017Artículo de revistahttp://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85Colombia111Volumen 76Archives of Public HealthMattar S, Tique V, Miranda J, Montes JE, Garzon D. Undifferentiated tropical febrile illness in Córdoba, Colombia Not everything is dengue. J Infect Public Health. 2017;10:507–12. http://dx.doi.org/10.1016/j.jiph.2016.09.014.Mattar S, Ojeda C, Arboleda J, Arrieta G, Bosch I, Botia I, et al. Case report: microcephaly associated with Zika virus infection. Colombia BMC Infectious Diseases. 2017;17:423. https://doi.org/10.1186/s12879-017-2522-6.Pan American Health Organization / World Health Organization. Regional Zika Epidemiological Update (Americas) March 10, 2017. Washington, D.C. D.C. 20037, United States of America. 2017. http://www2.paho.org/hq/index. php?option=com_content&view=article&id=11599&Itemid=41691&lang=en. Accessed 23 Apr 2017.Pan American Health Organization / World Health Organization. Zika suspected and confirmed cases reported by countries and territories in the Americas Cumulative cases, 2015–2017. Updated as of 20 April 2017. Washington, D.C.: 2017. http://www2.paho.org/hq/index.php?option=com_ docman&task=doc_view&Itemid=270&gid=39552&lang=es.Instituto Nacional de Salud (Colombia). Boletin Epidemiologico Semanal. Semana epidemiológica número 40 de 2015. Bogota D.C. 2017. http://www.ins.gov.co/ boletin-epidemiologico/Boletn%20Epidemiolgico/2015%20Boletin% 20epidemiologico%20semana%2040.pdf. Accessed 3 Mar 2017.Instituto Nacional de Salud (Colombia). Semana epidemiológica número 52 de 2016. Bogotá, D.C.: 2017. http://www.ins.gov.co/boletin-epidemiologico/ Boletn%20Epidemiolgico/2016%20Bolet%C3%ADn%20epidemiol%C3% B3gico%20semana%2052%20-.pdf. Accessed 17 Feb 2017.Pacheco O, Beltrán M, Nelson CA, Valencia D, Tolosa N, Farr SL, Padilla AV, Tong VT, Cuevas EL, Espinosa-Bode A, et al. Zika virus disease in Colombia — preliminary report. N Engl J Med. 2016. doi: 10.1056/NEJMoa1604037.Parra B, Lizarazo J, Jiménez-Arango JA, Zea-Vera AF, González-Manrique G, Vargas J, Angarita JA, Zuñiga G, Lopez-Gonzalez R, Beltran CL, et al. Guillain–Barré syndrome associated with Zika virus infection in Colombia. N Engl J Med. 2016;375:1513–23.Cuevas EL, Tong VT, Rozo N, Valencia D, Pacheco O, Gilboa SM, et al. Preliminary report of microcephaly potentially associated with Zika virus infection during pregnancy — Colombia, January–November 2016. MMWR Morb Mortal Wkly Rep. 2016;65:1409–13.Camacho E, Paternina-Gomez M, Blanco PJ, Osorio JE, Aliota MT. Detection of autochthonous Zika virus transmission in Sincelejo, Colombia. Emerg Infect Dis. 2016;22:927–9.Rojas DP, Dean NE, Yang Y, Kenah E, Quintero J, Tomasi S, Ramirez EL, Kelly Y, Castro C, Carrasquilla G, et al. The epidemiology and transmissibility of Zika virus in Girardot and San Andres island, Colombia, September 2015 to January 2016. Euro Surveill. 2016;21. http://dx.doi.org/10.2807/1560-7917.ES.2016.21.28.30283.Towers S, Brauer F, Castillo-Chavez C, Falconar AK, Mubayi A, Romero-Vivas CM. Estimate of the reproduction number of the 2015 Zika virus outbreak in Barranquilla, Colombia, and estimation of the relative role of sexual transmission. Epidemics. 2016;17:50–5.Instituto Nacional de Salud (Colombia). Boletín Epidemiológico. Bogotá, D. C.: 2017. http://www.ins.gov.co/boletin-epidemiologico/Paginas/default.aspx. Accessed 12 Feb 2017.Ministerio de Salud y Protección Social - Instituto Nacional de Salud (Colombia). Circular conjunta externa N° 00000061 de 2015. Vigilancia de la fiebre por virus Zika (ZIKV) en su fase II epidémica y fortalecimiento de la prevencion de la fiebre por virus Zika en grupos de riesgo. Bogotá, D.C.: 2017. http://www.ins.gov.co/Noticias/ZIKA/Circular%20Conj%20061%202015%20 Fiebre%20zika.pdf. Accessed 12 Feb 2017.Ministerio de Salud y Protección Social - Instituto Nacional de Salud (Colombia). Protocolo de vigilancia en salud pública: enfermedad por virus Zika. Bogotá, D.C; 2017. http://bvs.minsa.gob.pe/local/MINSA/3449.pdf. Accesed 14 Jul 2017Departamento Administrativo Nacional de Estadística (DANE, Colombia). Catálogo de Objetos Geográficos del Marco Geoestadístico Nacional. Dirección de Geoestadística, 2014. Bogotá, D.C.: 2017. http://www.dane.gov.co/. Accessed 19 Sept 2017.Departamento Administrativo Nacional de Estadística (DANE, Colombia). Estadísticas vitales nacimientos y defunciones. Bogotá, D.C.: 2017. https:// www.dane.gov.co/index.php/estadisticas-por-tema/demografia-y-poblacion/ nacimientos-y-defunciones. Accessed 18 Sept 2017.Departamento Administrativo Nacional de Estadística (DANE, Colombia). Catálogo de Objetos Geográficos del Marco Geoestadístico Nacional. Dirección de Geoestadística, 2014. Bogotá, D.C.: 2017. http://www.dane.gov.co/. Accessed 18 Sept 2017.Kloog I, Haim A, Portnov BA. Using kernel density function as an urban analysis tool: investigating the association between nightlight exposure and the incidence of breast cancer in Haifa, Israel. Comput Environ Urban Syst. 2009;33:55–63.Saunders C, Gammerman A, Vovk V. Ridge regression learning algorithm in dual variables. En (ICML-1998) Proceedings of the 15th International Conference on Machine Learning. Morgan Kaufmann. 1998:515–21.Pan American Health Organization / World Health Organization. Zika suspected and confirmed cases reported by countries and territories in the Americas Cumulative cases, 2015–2017. Updated as of 13 July 2017. Washington, D.C.: 2017. http://www.paho.org/hq/index.php?option=com_docman&task=doc_ view&Itemid=270&gid=40858&lang=es. Accessed 14 Jul 2017.Rojas DP, Dean NE, Yang Y, Kenah E, Quintero J, Tomasi S, et al. The epidemiology and transmissibility of Zika virus in Girardot and San Andres island, Colombia, September 2015 to January 2016. Euro Surveill. 2016;21(28). doi: 10.2807/1560-7917.ES.2016.21.28.30283.Jimenez Corona ME, De la Garza Barroso AL, Rodriguez Martínez JC, et al. Clinical and Epidemiological Characterization of Laboratory-Confirmed Autochthonous Cases of Zika Virus Disease in Mexico. PLoS Currents. 2016;8:ecurrents.outbreaks.a2fe1b3d6d71e24ad2b5afe982824053. doi:https:// doi.org/10.1371/currents.outbreaks.a2fe1b3d6d71e24ad2b5afe982824053.Oviedo-Pastrana M, Méndez N, Mattar S, Arrieta G, Gomezcaceres L. Epidemic outbreak of chikungunya in two neighboring towns in the Colombian Caribbean: a survival analysis. Archives of Public Health. 2017;75:1. doi: 10.1186/s13690-016-0169-1.Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika virus and birth defects — reviewing the evidence for causality. N Engl J Med. 2016;374:1981–7.Ministerio de Salud y Protección Social (Colombia). Lineamientos para la detección y manejo clínico integral de anomalías congénitas en fetos expuestos al virus del Zika durante la gestación de pacientes en Colombia. Bogotá, D.C.: 2017. https://www.minsalud.gov.co/sites/rid/Lists/ BibliotecaDigital/RIDE/VS/PP/ET/linea-deteccion-manejo-clinico-anomaliacongenitas-fotos-zika.pdf. Accessed 3 Mar 2017.Center for Disease Control and Prevention. CDC and the Instituto Nacional de Salud of Colombia collaborate to understand long-term effects of Zika virus infection during pregnancy. Atlanta.: 2017. https://www.cdc.gov/media/releases/ 2016/p0902-cdc-colombia-collaboration.html. Accessed 18 Sept 2017.Center for Disease Control and Prevention. Microcephaly & Other Birth Defects. Atlanta.: 2017. https://www.cdc.gov/zika/healtheffects/birth_defects.html. 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Thumbnailimage/jpeg13451https://repositorio.cecar.edu.co/bitstreams/bf3e7a68-dce0-47a3-a946-023b8ebfd62a/download87483853930729ea88b798b746ff8664MD54falseAnonymousREADcecar/10894oai:repositorio.cecar.edu.co:cecar/108942025-09-09 03:00:28.59https://creativecommons.org/licenses/by-nc/4.0/Derechos reservados - Corporación Universitaria de Caribe - CECARopen.accesshttps://repositorio.cecar.edu.coRepositorio Digital de la Corporación Universitaria Del Caribe 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