Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.
Bibliographical noteFunding Information:
We thank Funda??o Oswaldo Cruz in Bahia and Pernambuco states, University of S?o Paulo, Instituto Evandro Chagas, and the Brazilian Zika virus surveillance network for their essential contributions. We thank the following for giving us permission to use their unpublished genomes available on GenBank: R. Lanciotti, J. Lednicky, A. Enfissi, F. Baldanti, R. Shabman, B. Picket, R. Schinazi, M. Bonaldo, M. Gale, M. Capobianchi and C. Concetta, M. Leguia, J. Alberto Diaz, E. Sevilla-Reyes, A. Franz, M. Garcia- Blanco and M. J. van Hemert. We thank P. Fernando da Costa Vasconcelos, S. Guerreiro Rodrigues, J. Cardoso, J. Vasconcelos, J. Vianez Jr, J. Gil Melga?o, J. Blumel, M. C. Brito Lobato, L. Nunes Fava, C. Ayres, L. Abade and F. Campos. L.C.J.A. thanks QIAGEN for reagents and equipment and M.R.T.N. thanks FERPEL for consumables. We thank Oxford Nanopore for technical support, particularly R. Dokos, Z. McDougall, S. Cowan, G. Sanghera, and O. Hartwell. This work was supported by an MRC/Wellcome Trust/Newton Fund Zika Rapid Response grant (MC-PC-15100/ZK/16-078) and by the USAID Emerging Pandemic Threats Program-2 PREDICT-2 (Cooperative Agreement AID-OAA-A-14-00102). N.J.L. is supported by an MRC Bioinformatics Fellowship. N.R.F. is funded by a Sir Henry Dale Fellowship (grant 204311/Z/16/Z). CNPq contributed to trip expenses (grant 457480/2014-9). A.C.d.C. was supported by FAPESP #2012/03417-7 and M.R.T.N. by CNPq grant no. 302584/2015-3. A.B. and T.B. were supported by NIH award R35 GM119774. A.B. is supported by the NSF Graduate Research Fellowship Program (grant DGE-1256082). T.B. is a Pew Biomedical Scholar. C.Y.C. is partially supported by NIH grant R01 HL105704 and an award from Abbott Laboratories, Inc. E.C.H. is supported by a National Health and Medical Research Council Australia Fellowship (GNT1037231). C.-H.W. is supported by the MRC and CRUK (ANR00310) and by the Wellcome Trust and Royal Society (grant 101237/Z/13/Z). S.C.H. is supported by the Wellcome Trust. This research received funding from the ERC under grant agreements 614725-PATHPHYLODYN and 278433-PREDEMICS, and from EU Horizon 2020 under agreements 643476-COMPARE and 734548-ZIKAlliance. T.J. and E.T.M. acknowledge funding from IDAMS, DENFREE, DengueTools, and PPSUSFACEPE (project APQ-0302-4.01/13). R.F.F. received funding from FACEPE (APQ- 0044.2.11/16 and APQ-0055.2.11/16) and from CNPq (439975/2016-6). S.A.B. was supported by the Sicherheit von Blut und Geweben hinsichtlich der Abwesenheit von Zikaviren from the German Ministry of Health.
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