Send to

Choose Destination
Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):10762-10767. doi: 10.1073/pnas.1809253115. Epub 2018 Sep 28.

Dynamics and determinants of the force of infection of dengue virus from 1994 to 2015 in Managua, Nicaragua.

Author information

Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA 94720-3370.
Department of Integrative Biology, University of California, Berkeley, CA 94720.
Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua 16064.
Sustainable Sciences Institute, Managua, Nicaragua 14007.
School of Medicine, University of California, San Francisco, CA 94143.
Centro de Salud Sócrates Flores Vivas, Ministry of Health, Managua, Nicaragua 12014.
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109.
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA 94720-3370;


Dengue virus (DENV) is the most prevalent human vector-borne viral disease. The force of infection (FoI), the rate at which susceptible individuals are infected in a population, is an important metric for infectious disease modeling. Understanding how and why the FoI of DENV changes over time is critical for developing immunization and vector control policies. We used age-stratified seroprevalence data from 12 years of the Pediatric Dengue Cohort Study in Nicaragua to estimate the annual FoI of DENV from 1994 to 2015. Seroprevalence data revealed a change in the rate at which children acquire DENV-specific immunity: in 2004, 50% of children age >4 years were seropositive, but by 2015, 50% seropositivity was reached only by age 11 years. We estimated a spike in the FoI in 1997-1998 and 1998-1999 and a gradual decline thereafter, and children age <4 years experienced a lower FoI. Two hypotheses to explain the change in the FoI were tested: (i) a transition from introduction of specific DENV serotypes to their endemic transmission and (ii) a population demographic transition due to declining birth rates and increasing life expectancy. We used mathematical models to simulate these hypotheses. We show that the initial high FoI can be explained by the introduction of DENV-3 in 1994-1998, and that the overall gradual decline in the FoI can be attributed to demographic shifts. Changes in immunity and demographics strongly impacted DENV transmission in Nicaragua. Population-level measures of transmission intensity are dynamic and thus challenging to use to guide vaccine implementation locally and globally.


Nicaragua; cohort study; dengue virus; force of infection; transmission intensity

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center