title: Unusual dengue virus 3 epidemic in Nicaragua, 2009.
abstract: The four dengue virus serotypes (DENV1-4) cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric dengue in Managua. From August 2009-January 2010, 212 dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital. In our parallel community-based cohort study, 170 dengue cases were recorded in 2009-10, compared to 13-65 cases in 2004-9. In both studies, significantly more patients experienced "compensated shock" (poor capillary refill plus cold extremities, tachycardia, tachypnea, and/or weak pulse) in 2009-10 than in previous years (42.5% [90/212] vs. 24.7% [82/332] in the hospital study (p<0.001) and 17% [29/170] vs. 2.2% [4/181] in the cohort study (p<0.001). Signs of poor peripheral perfusion presented significantly earlier (1-2 days) in 2009-10 than in previous years according to Kaplan-Meier survival analysis. In the hospital study, 19.8% of subjects were transferred to intensive care, compared to 7.1% in previous years - similar to the cohort study. DENV-3 predominated in 2008-9, 2009-10, and 2010-11, and full-length sequencing revealed no major genetic changes from 2008-9 to 2010-11. In 2008-9 and 2010-11, typical dengue was observed; only in 2009-10 was unusual presentation noted. Multivariate analysis revealed only "2009-10" as a significant risk factor for Dengue Fever with Compensated Shock. Interestingly, circulation of pandemic influenza A-H1N1 2009 in Managua was shifted such that it overlapped with the dengue epidemic. We hypothesize that prior influenza A H1N1 2009 infection may have modulated subsequent DENV infection, and initial results of an ongoing study suggest increased risk of shock among children with anti-H1N1-2009 antibodies. This study demonstrates that parameters other than serotype, viral genomic sequence, immune status, and sequence of serotypes can play a role in modulating dengue disease outcome.
authors.affiliation: Sustainable Sciences Institute, Managua, Nicaragua.
authors.forename: Gamaliel
authors.initials: G
authors.lastname: Gutierrez
authors.forename: Katherine
authors.initials: K
authors.lastname: Standish
authors.forename: Federico
authors.initials: F
authors.lastname: Narvaez
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Perez
authors.forename: Saira
authors.initials: S
authors.lastname: Saborio
authors.forename: Douglas
authors.initials: D
authors.lastname: Elizondo
authors.forename: Oscar
authors.initials: O
authors.lastname: Ortega
authors.forename: Andrea
authors.initials: A
authors.lastname: Nuñez
authors.forename: Guillermina
authors.initials: G
authors.lastname: Kuan
authors.forename: Angel
authors.initials: A
authors.lastname: Balmaseda
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000150:complications / Q000453:epidemiology* / Q000473:pathology* / Q000821:virology; D003716:Dengue Virus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D004196:Disease Outbreaks; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009527:Nicaragua / Q000453:epidemiology; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D012703:Serotyping; D012769:Shock / Q000453:epidemiology*
chemical_list: D012367:RNA, Viral
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