Index Cluster Study of Dengue Virus Infection in Nicaragua

Miguel Reyes Socrates Flores Vivas Health Center, Ministry of Health, Managua, Nicaragua; Departamento de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California

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Juan Carlos Mercado Socrates Flores Vivas Health Center, Ministry of Health, Managua, Nicaragua; Departamento de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California

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Katherine Standish Socrates Flores Vivas Health Center, Ministry of Health, Managua, Nicaragua; Departamento de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California

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Juan Carlos Matute Socrates Flores Vivas Health Center, Ministry of Health, Managua, Nicaragua; Departamento de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California

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Oscar Ortega Socrates Flores Vivas Health Center, Ministry of Health, Managua, Nicaragua; Departamento de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California

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Berman Moraga Socrates Flores Vivas Health Center, Ministry of Health, Managua, Nicaragua; Departamento de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California

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William Avilés Socrates Flores Vivas Health Center, Ministry of Health, Managua, Nicaragua; Departamento de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California

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Matthew R. Henn Socrates Flores Vivas Health Center, Ministry of Health, Managua, Nicaragua; Departamento de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California

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Angel Balmaseda Socrates Flores Vivas Health Center, Ministry of Health, Managua, Nicaragua; Departamento de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California

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Guillermina Kuan Socrates Flores Vivas Health Center, Ministry of Health, Managua, Nicaragua; Departamento de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California

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Eva Harris Socrates Flores Vivas Health Center, Ministry of Health, Managua, Nicaragua; Departamento de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California

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Traditional study designs do not identify acute asymptomatic or pre-symptomatic dengue virus (DENV) infections, thus limiting our understanding of immunologic and viral factors that modulate infection outcome. In the 2006 and 2007 dengue seasons, we conducted a pilot index cluster study in Managua, Nicaragua, in which 442 persons living within 50 meters of 22 index cases identified through an ongoing pediatric cohort study were evaluated for DENV infection. Post-enrollment and pre-enrollment DENV infections were confirmed in 12 (2.7%) and 19 (4.3%) contacts, respectively. Five (42%) post-enrollment infections were asymptomatic, and DENV-2 was identified in 9 (75%) infections. Phylogenetic analysis with full-length DENV genomic sequence from contacts, index cases, and cohort dengue cases indicated focal transmission and infection outside the local area. We demonstrate the feasibility of identification of acute asymptomatic and pre-symptomatic cases in urban Latin America, the first report of such a study in the Americas, and identify age and concomitant immunity to DENV of contacts as a key factor in index cluster study design.

Author Notes

*Address correspondence to Eva Harris, Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, 1 Barker Hall, Berkeley, CA 94720-7354. E-mail: eharris@berkeley.edu
†These authors contributed equally to this study.

Financial support: This study was supported by the Pediatric Dengue Vaccine Initiative (grant #VE-1) and was supported in part with federal funds from the National Institute of Allergy and Infectious Disease, National Institutes of Health, Department of Health and Human Services, under contracts HHSN266200400001C (Broad) and HHSN272200900006C (Broad).

Authors' addresses: Miguel Reyes and Guillermina Kuan, Centro de Salud Sócrates Flores Vivas, Barrio Monseñor Lezcano, Managua, Nicaragua. Juan Carlos Mercado, Juan Carlos Matute, Berman Moraga, and Angel Balmaseda, Departamento de Virología, Centro Nacional de Diagnóstico y Referencia, Ministerio de Salud, Complejo de Salud Dra. Concepcion Palacios, Primero de Mayo, Managua, Nicaragua. Katherine Standish, Oscar Ortega, and William Avilés, Sustainable Sciences Institute, c/o Centro de Salud Sócrates Flores Vivas, Barrio Monseñor Lezcano, Managua, Nicaragua. Matthew R. Henn, The Broad Institute of Harvard and MIT, Cambridge, MA. Eva Harris, Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA.

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