Genomic Epidemiology Reconstructs the Introduction and Spread of Zika Virus in Central America and Mexico

Julien Thézé, Tony Li, Louis du Plessis, Jerome Bouquet, Moritz U.G. Kraemer, Sneha Somasekar, Guixia Yu, Mariateresa de Cesare, Angel Balmaseda, Guillermina Kuan, Eva Harris, Chieh hsi Wu, M. Azim Ansari, Rory Bowden, Nuno R. Faria, Shigeo Yagi, Sharon Messenger, Trevor Brooks, Mars Stone, Evan M. BlochMichael Busch, José E. Muñoz-Medina, Cesar R. González-Bonilla, Steven Wolinsky, Susana López, Carlos F. Arias, David Bonsall, Charles Y. Chiu*, Oliver G. Pybus

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

The Zika virus (ZIKV) epidemic in the Americas established ZIKV as a major public health threat and uncovered its association with severe diseases, including microcephaly. However, genetic epidemiology in some at-risk regions, particularly Central America and Mexico, remains limited. We report 61 ZIKV genomes from this region, generated using metagenomic sequencing with ZIKV-specific enrichment, and combine phylogenetic, epidemiological, and environmental data to reconstruct ZIKV transmission. These analyses revealed multiple independent ZIKV introductions to Central America and Mexico. One introduction, likely from Brazil via Honduras, led to most infections and the undetected spread of ZIKV through the region from late 2014. Multiple lines of evidence indicate biannual peaks of ZIKV transmission in the region, likely driven by varying local environmental conditions for mosquito vectors and herd immunity. The spatial and temporal heterogeneity of ZIKV transmission in Central America and Mexico challenges arbovirus surveillance and disease control measures. Thézé et al. examine the genomic epidemiology of Zika virus in Central America and Mexico. Following its likely introduction to Honduras in 2014, the virus spread undetected in the region. Genetic and epidemiological data indicate that biannual transmission peaks occurred, and could potentially be explained by local variation in mosquito abundance.

Original languageEnglish (US)
Pages (from-to)855-864.e7
JournalCell Host and Microbe
Volume23
Issue number6
DOIs
StatePublished - Jun 13 2018

Funding

We thank Marco A. Espinoza for processing the Mexican ZIKV serum samples. We thank Magelda Montoya and Juan Carlos Mercado for their invaluable assistance in providing samples from Nicaragua. We also thank Prof. Nicholas Loman and Joshua Quick for their feedback on the manuscript. We are grateful to past and present members of the team at the Centro de Salud S\u00F3crates Flores Vivas, the National Virology Laboratory in the Centro Nacional de Diagn\u00F3stico y Referencia, and the Sustainable Sciences Institute in Nicaragua for their dedication and high-quality work, as well as the children who participated in the studies and their families. We thank Philippe Lemey for providing the script to analyze viral transmissions among locations. We thank Paul Klenerman, who supported sequencing of the Nicaragua samples through the Oxford Viromics initiative. This work was supported by the European Research Council under the European Commission Seventh Framework Program ( FP7/2007-2013 )/European Research Council grant agreement 614725-PATHPHYLODYN and by the Oxford Martin School . M.U.G.K. is supported by the Society in Science Branco Weiss Fellowship, administered by the ETH Zurich, and acknowledges funding from a training grant from the National Institute of Child Health and Human Development ( T32HD040128 ) and the National Library of Medicine of the NIH ( R01LM010812 , R01LM011965 ). N.R.F. is supported by the Wellcome Trust and the Royal Society ( 204311/Z/16/Z ). This work was also funded in part by Abbott Laboratories (C.Y.C.), NIH grants R01AI099631 (A.B.), P01AI106695 (E.H.), U19 AI118610 (S.W. and E.H.), and R21AI129455 (C.Y.C.) from the National Institute of Allergy and Infectious Diseases, and NIH grant R01 HL105704 (C.Y.C.) from the National Heart, Lung, and Blood Institute. This work was also supported by the Wellcome Trust core award (203141/Z/16/Z). We thank Marco A. Espinoza for processing the Mexican ZIKV serum samples. We thank Magelda Montoya and Juan Carlos Mercado for their invaluable assistance in providing samples from Nicaragua. We also thank Prof. Nicholas Loman and Joshua Quick for their feedback on the manuscript. We are grateful to past and present members of the team at the Centro de Salud S?crates Flores Vivas, the National Virology Laboratory in the Centro Nacional de Diagn?stico y Referencia, and the Sustainable Sciences Institute in Nicaragua for their dedication and high-quality work, as well as the children who participated in the studies and their families. We thank Philippe Lemey for providing the script to analyze viral transmissions among locations. We thank Paul Klenerman, who supported sequencing of the Nicaragua samples through the Oxford Viromics initiative. This work was supported by the European Research Council under the European Commission Seventh Framework Program (FP7/2007-2013)/European Research Council grant agreement 614725-PATHPHYLODYN and by the Oxford Martin School. M.U.G.K. is supported by the Society in Science Branco Weiss Fellowship, administered by the ETH Zurich, and acknowledges funding from a training grant from the National Institute of Child Health and Human Development (T32HD040128) and the National Library of Medicine of the NIH (R01LM010812, R01LM011965). N.R.F. is supported by the Wellcome Trust and the Royal Society (204311/Z/16/Z). This work was also funded in part by Abbott Laboratories (C.Y.C.), NIH grants R01AI099631 (A.B.), P01AI106695 (E.H.), U19 AI118610 (S.W. and E.H.), and R21AI129455 (C.Y.C.) from the National Institute of Allergy and Infectious Diseases, and NIH grant R01 HL105704 (C.Y.C.) from the National Heart, Lung, and Blood Institute. This work was also supported by the Wellcome Trust core award (203141/Z/16/Z).

Keywords

  • Central America
  • Mexico
  • Zika virus
  • bait capture enrichment
  • effective reproductive number
  • genomics
  • metagenomic sequencing
  • phylodynamics
  • transmission
  • “spiked” primer enrichment

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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