Unusual Dengue Virus 3 Epidemic in Nicaragua, 2009 e1394

• Published in: PLoS neglected tropical diseases Vol. 5; no. 11
• Main Authors: Gutierrez, Gamaliel, Standish, Katherine, Narvaez, Federico, Perez, Maria Angeles, Saborio, Saira, Elizondo, Douglas, Ortega, Oscar, Nuñez, Andrea, Kuan, Guillermina, Balmaseda, Angel, Harris, Eva
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 01-11-2011
• Subjects: Dengue fever; Epidemics; Extremities; Hospitals; Hypotheses; Immune status; Intensive care; Multivariate analysis; Pandemics; Pediatrics; Risk factors; Studies; Survival analysis; Tropical diseases; Vector-borne diseases; Viral diseases; Nicaragua
• ISSN: 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0001394

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.