Establishment and cryptic transmission of Zika virus in Brazil and the Americas

Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil1. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 20162) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 20162). 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 disease3. 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

Establishment and cryptic transmission of Zika virus in Brazil and the Americas

University of Oxford. Department of Zoology, Oxford, UK / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.University of Birmingham. Institute of Microbiology and Infection. Birmingham, UK.University of Oxford. Department of Zoology. Oxford UK.University of Oxford. Department of Zoology. Oxford, UK / Harvard Medical School. Boston, MA, USA / Boston Children's Hospital. Boston, MA, USA.University of Oxford. Department of Zoology. Oxford, UK.Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA / University of Washington. Department of Epidemiology. Seattle, WA, USA.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.University of Oxford. Department of Statistics. Oxford, UK.University of Oxford. Department of Zoology. Oxford, UK.Institut Pasteur. Biostatistics and Integrative Biology. Mathematical Modelling of Infectious Diseases and Center of Bioinformatics. Paris, FR / Centre National de la Recherche Scientifique. Paris, FR.University of Oxford. Department of Zoology. Oxford, UK.Ministry of Health. Coordenação dos Laboratórios de Saúde. Brasília, DF, Brazil.Ministry of Health. Coordenação Geral de Vigilância e Resposta às Emergências em Saúde Pública. Brasília, DF, Brazil / Fundação Oswaldo Cruz. Center of Data and Knowledge Integration for Health. Salvador, BA, Brazil.Ministry of Health. Departamento de Vigilância das Doenças Transmissíveis. Brasilia, DF, Brazil.Ministry of Health. Coordenação Geral dos Programas de Controle e Prevenção da Malária e das Doenças Transmitidas pelo Aedes. Brasília, DF, Brazil / Pan American Health Organization (PAHO). Buenos Aires, AR.Ministry of Health. Coordenação Geral dos Programas de Controle e Prevenção da Malária e das Doenças Transmitidas pelo Aedes. Brasília, DF, Brazil / Fundação Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.Ministry of Health. Coordenação Geral dos Programas de Controle e Prevenção da Malária e das Doenças Transmitidas pelo Aedes. Brasília, DF, BrazilMinistry of Health. Departamento de Vigilância das Doenças Transmissíveis. Brasilia, DF, Brazil.Ontario Institute for Cancer Research. Toronto, ON, Canada.University of Nottingham. Nottingham, UKThe Scripps Research Institute. Department of Immunology and Microbial Science. La Jolla, CA, USA.The Scripps Research Institute. Department of Immunology and Microbial Science. La Jolla, CA, USA.University of California. Departments of Laboratory Medicine and Medicine & Infectious Diseases. San Francisco, CA, USA.University of California. Departments of Laboratory Medicine and Medicine & Infectious Diseases. San Francisco, CA, USA.Instituto Mexicano del Seguro Social. División de Laboratorios de Vigilancia e Investigación Epidemiológica. Ciudad de México, MC.Instituto Mexicano del Seguro Social. División de Laboratorios de Vigilancia e Investigación Epidemiológica. Ciudad de México, MC.Universidad Nacional Autónoma de México. Instituto de Biotecnología. Cuernavaca, MC.Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.Paul-Ehrlich-Institut. Langen, Germany.Laboratório Central de Saúde Pública Noel Nutels. Rio de Janeiro, RJ, Brazil.Laboratório Central de Saúde Pública Noel Nutels. Rio de Janeiro, RJ, Brazil.Laboratório Central de Saúde Pública Noel Nutels. Rio de Janeiro, RJ, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Fundação Oswaldo Cruz. Salvador, BA, Brazil.Laboratório Central de Saúde Pública. Natal, RN, Brazil.Laboratório Central de Saúde Pública. Natal, RN, Brazil / Universidade Potiguar. Natal, RN, Brazil.Laboratório Central de Saúde Pública. Natal, RN, Brazil / Faculdade Natalense de Ensino e Cultura. Natal, RN, Brazil.Laboratório Central de Saúde Pública. João Pessoa, PB, Brazil.Laboratório Central de Saúde Pública. João Pessoa, PB, Brazil.Laboratório Central de Saúde Pública. João Pessoa, PB, Brazil.Laboratório Central de Saúde Pública. João Pessoa, PB, Brazil.Fundação Oswaldo Cruz. Recife, PE, Brazil.Fundação Oswaldo Cruz. Recife, PE, Brazil.Fundação Oswaldo Cruz. Recife, PE, Brazil / Colorado State University. Department of Microbiology, Immunology &Pathology. Fort Collins, CO, USA.Fundação Oswaldo Cruz. Recife, PE, Brazil.Heidelberg University Hospital. Department for Infectious Diseases. Section Clinical Tropical Medicine. Heidelberg, Germany.Fundação Oswaldo Cruz. Recife, PE, Brazil.Laboratório Central de Saúde Pública. Maceió, AL, Brazil.Laboratório Central de Saúde Pública. Maceió, AL, Brazil.Laboratório Central de Saúde Pública. Maceió, AL, Brazil.Universidade Estadual de Feira de Santana. Feira de Santana, BA, Brazil.Secretaria de Saúde de Feira de Santana. Feira de Santana, BA, Brazil.Universidade Federal do Amazonas. Manaus, AM, Brazil.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.Hospital São Francisco. Ribeirão Preto, SP, Brazil.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.Universidade Federal do Tocantins. Palmas, TO, Brazil.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.University of Sydney. Sydney, Australia.University of Edinburgh. Institute of Evolutionary Biology. Edinburgh, UK / National Institutes of Health. Fogarty International Center. Bethesda, MD, USA.Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.Fundação Oswaldo Cruz. Salvador, BA, Brazil.University of Birmingham. Institute of Microbiology and Infection. Birmingham, UK.University of Oxford. Department of Zoology, Oxford, UK / Metabiota. San Francisco, CA, USA.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.Fundação Oswaldo Cruz. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Salvador, BA, Brazil / University of Rome Tor Vergata. Rome, Italy.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