Doodle by Elisa Visher This October, post-doc Saki Takahashi visited our seminar from across the bay to present her work on "Characterizing re-emergence patterns of dengue in Brazil". Saki recently started her post-doc after finishing up her PhD with Jess Metcalf at Princeton. Saki is broadly interested in how immunity drives transmission dynamics in multi-strain pathogen systems. For many infectious diseases, we know that hosts develop immunity after infection. However, this immunity can vary in how long-lived it is, how strong it is, and how broad it is, with all of these variables shaping how immunity influences disease dynamics. Saki uses modelling techniques to elucidate patterns of transmission from epidemiological data. Specifically, Saki build these models with age-structured case incidence data, as it can be especially informative in teasing apart patterns of immunity, strain dynamics, and transmission. This age-structured data can be important because shifts in the age distribution of cases can indicate changes in the distribution of susceptibles and the force of infection of different strains. For the project that she presented to us at the Berkeley EEID seminar, Saki looked at dengue dynamics in Brazil. Dengue is an arboviral disease that has recently re-emerged in Brazil. Globally, it is the most rapidly spreading arboviral disease because of its multiple serotypes, increased dispersion of its vector, urbanization, and global travel. Dengue has four antigenically distinct but interacting serotypes. Humans can be infected by multiple of these serotypes because infection with each strain does not offer complete immunity against others. However, previous infection with a different stain of dengue does change the clinical symptoms of infection. People normally have worse symptoms during their second infection (including dengue fever and dengue hemorrhagic fever), after generally asymptomatic primary infections. In Thailand, where all four strains are endemic, dengue is generally considered a childhood disease because each strain’s force of infection is high enough that people tend to be infected by multiple strains and have clinically symptomatic dengue infection during childhood. However, Thailand has recently had a demographic transition with people living longer and having fewer children, which has decreased this force of infection and led to the average age of cases being older. This illustrates how the age-structured case data that Saki uses can be hugely informative for understanding the transmission dynamics of multi-strain pathogens like dengue. Saki, therefore, turned her attention to using such age-structured data to model dengue dynamics in Brazil, where dengue has been re-emerging since 1986 due to the re-emergence of its mosquito host, Aedes aegypti, in the 1970s. Recently, in 2007, clinical cases of dengue have shifted from mostly being seen in adults to mostly being seen in children. Saki therefore wanted to ask whether she could build a model to capture dengue’s reemergence and temporal variation of transmission in Brazil and use it to identify factors that could explain the shift in the age-distribution of cases. Saki and colleagues built models fit to age-structured epidemiological data which used time varying forces of infection to allow for the unequal circulation of serotypes over time, accounted for the different clinical symptoms of primary and secondary infections, and allowed for differences in reporting rates. The models could also capture finer spatial scales, such as regions within states. From these models, they were able to test between hypotheses to clarify possible causes of the demographic shift in dengue epidemiology over time. They find good support that the shift in the age distribution of cases was driven by the re-emergence of the dengue 2 serotype in 2007, especially in Brazil’s north east states. Basically, before the re-emergence of dengue 2, children likely had asymptomatic first infections, but did not have secondary infections leading to clinical manifestations until adulthood. After 2007, the renewed circulation of dengue 2 led to increased forces of infection and individuals were getting infected with their second serotype of dengue during childhood. In summary, data on the age distribution of cases can be used to yield insights into population susceptibility and disease dynamics. Models using this data suggest that the 2007 shift in the age distribution of cases in Brazil was due to the re-emergence of dengue 2. This may suggest that age-dependent clinical guidelines should developed to reflect changing age burdens. Finally, Saki thinks that one of the next steps for this project is to validate the model with environmental variation data, more epidemiological surveillance data, and more orthogonal data. She also wants to do simulations and modelling on time to endemicity to get an understanding of the epidemiological transmission from reemergence to endemicity. Summary by Elisa Visher
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7/29/2023 11:21:45 am
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7/29/2023 04:15:44 pm
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