Ministry of Health, Managua, Nicaragua
UC Berkeley, School of Public Health
U.S. Based Mentors
Eva Harris, PhD
Professor, Division of Infectious Diseases and Vaccinology; Director, Center for Global Public Health
Dengue; Influenza transmission
Site and Background
These projects are based on over two decades of collaboration between Dr. Eva Harris at UC Berkeley and the Nicaraguan Ministry of Health; specificially, the Centro Nacional de Diagnóstico y Referencia, directed by Dr. Angel Balmaseda; the Infectious Diseases Unit of the National Pediatric Reference Hospital, Hospital Infantil Manuel de Jesús Rivera (HIMJR); and the Centro de Salud Sócrates Flores Vivas (HCSFV), The HIMJR is the site of a 14-year ongoing hospital-based study of biological, immunolgical, and clinical aspects of severe dengue, and the HCSFV is the site of the 8-year Pediatric Dengue Cohort Study and the 5-year Nicaraguan Influenza Cohort Study, both of which are ongoing.
1. Hospital-based Study in the HIMJR, Managua (2005-present): This study of pediatric dengue is based at the National Pediatric Reference Hospital in Managua. Children suspected of having dengue are enrolled during the dengue season each year, and blood samples are collected for 3 consecutive days during the acute phase of illness, at convalescence, and at 3, 6, 12, and 18 months. Acute samples are used for clinical laboratory tests and for dengue diagnosis via molecular biological, virological, and serological methods at the National Virology Laboratory. Extensive longitudinal data regarding the clinical course of disease are recorded, monitored, and digitized. Serum, virus and viral RNA, peripheral blood mononuclear cells, and DNA are used for analysis of gene expression; B cell phenotype, antibody characteristics and repertoire (immunoprofiling); development of novel diagnostics; host genetic studies, and studies of viral genetics and intrahost diversity ,among others. These studies are supported by several NIH grants (U54 AI065359, R21 AI100186).
2. Pediatric Dengue Cohort Study (2004-present): The PDCS is a community-based prospective cohort study established to study the natural history of pediatric dengue transmission and viral and host determinants of dengue immunity and pathogenesis. ~3,500 children receive all primary medical care from study physicians at the Socrates Flores Vivas Health Center in District II of Managua, and all appointment information is collected onto systematic data forms. Every year, healthy blood samples from all study children are collected to determine the annual incidence of dengue virus infection. The cohort study enables research on dengue epidemiology, immunology, diagnostics, phylogenetics, and modeling, as well as on overall burden of disease/co-morbidity and innovative eHealth/mHealth applications. The study is supported by NIH via an IRIDA (R01 AI099631) and a host genetics study (BAA-NIAID-DAIT-NIHAI2009061), among others.
3. Nicaragua Influenza Cohort Study (2007-present). Dr. Aubree Gordon at UC Berkeley, together with Dr. Harris and Nicaraguan colleagues, has led a pediatric influenza cohort study since 2007, forming a dual cohort study with the PDCS. The Nicaraguan Influenza Cohort Study examines the incidence, epidemiologic features, and transmission of influenza in children 0-14 years old. Children are enrolled prospectively, and data is systematically recorded at all medical visits. Parents are encouraged to bring their child to the study health center at the first sign of illness, and adherence is high. Influenza-like illness (ILI) cases are processed by RT-PCR, viral isolation is performed on all RT-PCR-positive samples, and full-length sequencing of virus is performed through the NIAID Influenza Genome Sequencing Project. This study forms the bases for epidemiological, viral, immunological, phylogenetic, and modeling studies of influenza. The site is supported by an ICIDR grant (U01 AI088654) and a CDC grant for an Influenza Birth Cohort.