The Role of Seroimmunological Interactions in Determining the Seasonality of Dengue Fever Outbreaks During Transient Periods of Serotype Invasion or Replacement

Abstract

Seasonal changes in climate undeniably contribute to the regularity of outbreaks of dengue in the tropics. Epidemics of dengue fever, however, do not occur with perfect regularity in areas where the disease is endemic, and during periods of serotype competition, other factors can determine the size and timing of outbreaks and the chance of one serotype replacing another. Part I of this paper discusses dengue history, worldwide incidence, and the seroimmunological and epidemiological properties that are unique to multi-serotype dengue dynamics and relevant to the disease’s seasonality. A Methods section following Part I introduces the data analysis and mathematical modeling techniques that will be used to support this paper’s conclusions. Part II analyzes case studies of dengue fever incidence data in three Latin American countries during short periods of serotypic competition or coexistence. A time series of dengue fever diagnoses in Iquitos, Peru from 2007 - 2009 documents the replacement of serotype DENV3 by DENV4, during which time there was a shift in the seasonality of disease incidence such that the peak week of the epidemic occurred earlier in the year after replacement. Case numbers from San Juan, Puerto Rico from 2009 - 2011 show a shift in seasonality during a period when two serotypes coexisted with minimal competition. Bulletins from the Brazilian Ministry of Health between 2014 - 2016 allow for an analysis of spatiotemporal dengue dynamics during a period of serotypic replacement accompanied by an asynchrony between serotypes. Part III uses simulations of a mathematical model of multi-serotype dengue transmission to investigate the factors that could theoretically allow for asynchrony between serotypes and changes in the timing of DENV outbreaks when multiple serotypes are present in a population. The statistical data analysis and mathematical modeling together illustrate that interactions between serotypes like antibody-dependent enhancement and cross-immunity can overpower seasonal drivers in determining the intensity and seasonality of dengue fever outbreaks.