The Perfect Storm of 2019: An immunological and phylodynamic analysis of Cambodia’s unprecedented dengue outbreak

Author:

Brook Cara E.,Li Yimei,Yek Christina,Northrup Graham R.,Lay Sreyngim,Chea Sophana,Ahyong Vida,Parker Daniel M.,Man Somnang,Pacheco Andrea R.ORCID,Mengheng Oum,Oliveira Fabiano,Fahsbender Liz,Leang Rithea,Huy Rekol,Huch Chea,Lon Chanthap,Tato Cristina M.,DeRisi Joseph L.,Boots Michael,Bohl Jennifer A.,Manning Jessica E.

Abstract

AbstractThe year 2019 witnessed the highest number of dengue cases ever reported globally. We analyzed epidemiological, serological, and phylogenomic data to investigate the drivers of the 2019 epidemic in Cambodia. Using epidemiological models fit to a 19-year national dataset, we identified an overall trend of declining annual force of infection (FOI) for dengue virus (DENV) in Cambodia, interspersed with FOI spikes corresponding to epidemic year caseloads that exceeded demographic predictions. We constructed time-resolved phylogenetic trees with 105 DENV genomes sequenced from the 2019 Cambodian epidemic, paired with historical Southeast Asian data, to document the first-recorded introduction of DENV-2 Cosmopolitan genotype into Cambodia. This introduction yielded highly localized transmission and decreased genomic diversity when compared to endemic DENV-1, supporting the hypothesis of epidemic invasion. Introduction of this genetically distinct lineage into a population with limited prior immunity—paired with a spike in FOI—was a key driver of the 2019 Cambodian epidemic.These studies were registered at clinicaltrials.gov under NCT04034264 and NCT03534245.

Publisher

Cold Spring Harbor Laboratory

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