Biological Sciences Division
Published August 27, 2024 | Version v1
Journal article Open

Climate, demography, immunology, and virology combine to drive two decades of dengue virus dynamics in Cambodia

Creators

  • 1. University of Chicago
  • 2. York University
  • 3. National Institute of Allergy and Infectious Diseases
  • 4. Chan Zuckerberg Biohub
  • 5. Chan Zuckerberg Inititiative
  • 6. National Center for Parasitology, Entomology, and Malaria Control
  • 7. University of California, Berkeley
  • 8. University of California, Irvine
  • 9. University of Texas

Description

The incidence of dengue virus disease has increased globally across the past half-century, with highest number of cases ever reported in 2019 and again in 2023. We analyzed climatological, epidemiological, and phylogenomic data to investigate drivers of two decades of dengue in Cambodia, an understudied endemic setting. Using epidemiological models fit to a 19-y dataset, we first demonstrate that climate-driven transmission alone is insufficient to explain three epidemics across the time series. We then use wavelet decomposition to highlight enhanced annual and multiannual synchronicity in dengue cycles between provinces in epidemic years, suggesting a role for climate in homogenizing dynamics across space and time. Assuming reported cases correspond to symptomatic secondary infections, we next use an age-structured catalytic model to estimate a declining force of infection for dengue through time, which elevates the mean age of reported cases in Cambodia. Reported cases in >70-y-old individuals in the 2019 epidemic are best explained when also allowing for waning multitypic immunity and repeat symptomatic infections in older patients. We support this work with phylogenetic analysis of 192 dengue virus (DENV) genomes that we sequenced between 2019 and 2022, which document emergence of DENV-2 Cosmopolitan Genotype-II into Cambodia. This lineage demonstrates phylogenetic homogeneity across wide geographic areas, consistent with invasion behavior and in contrast to high phylogenetic diversity exhibited by endemic DENV-1. Finally, we simulate an age-structured, mechanistic model of dengue dynamics to demonstrate how expansion of an antigenically distinct lineage that evades preexisting multitypic immunity effectively reproduces the older-age infections witnessed in our data.

Data availability

Genome sequence data, Consensus DENV sequences, case counts and sequences data have been deposited in NCBI SRA (PRJNA681566) (52), Genbank (Accession Nos. reported in SI Appendix, Table S9), Zenodo Repository (https://zenodo.org/records/13308848) (80). All other data are included in the manuscript and/or supporting information; for access to sensitive public health information, including geolocations for specific cases, please contact the authors directly.

Files

brook-et-al-2024-climate-demography-immunology-and-virology-combine-to-drive-two-decades-of-dengue-virus-dynamics-in.pdf

Files (10.9 MB)

Additional details

Identifiers

DOI
10.1073/pnas.2318704121
Other
oai:uchicago.tind.io:13299

Funding

National Institute of Allergy and Infectious Diseases
Bill and Melinda Gates Foundation
OPP1211806
Bill and Melinda Gates Foundation
OPP1211841

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Ecology and Evolution