Viral genome-based Zika virus transmission dynamics in a paediatric cohort during the 2016 Nicaragua epidemic
Haoyang Sun,
Raquel A. Binder,
Borame Dickens,
Paola Florez de Sessions,
Maia A. Rabaa,
Eliza Xin Pei Ho,
Alex R Cook,
Fausto Bustos Carrillo,
Jairo Carey Monterrey,
Guillermina Kuan,
Angel Balmaseda,
Eng Eong Ooi,
Eva Harris,
October M. Sessions
Affiliations
Haoyang Sun
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore
Raquel A. Binder
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA; Sustainable Sciences Institute, Managua, Nicaragua
Borame Dickens
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore
Paola Florez de Sessions
Genome Institute of Singapore, A*STAR, Singapore, Singapore
Maia A. Rabaa
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine, Nuffield Department of Medicine, Oxford University, Oxford, UK
Eliza Xin Pei Ho
Genome Institute of Singapore, A*STAR, Singapore, Singapore
Alex R Cook
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore
Fausto Bustos Carrillo
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA; Sustainable Sciences Institute, Managua, Nicaragua
Jairo Carey Monterrey
Sustainable Sciences Institute, Managua, Nicaragua
Guillermina Kuan
Sustainable Sciences Institute, Managua, Nicaragua; Health Center Sócrates Flores Vivas, Ministry of Health, Managua, Nicaragua
Angel Balmaseda
Sustainable Sciences Institute, Managua, Nicaragua; Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua
Eng Eong Ooi
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Duke-NUS Medical School, Singapore, Singapore
Eva Harris
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA; Corresponding authors.
October M. Sessions
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Duke-NUS Medical School, Singapore, Singapore; Department of Pharmacy, National University of Singapore, Singapore; Corresponding authors.
Background: Nicaragua experienced a large Zika epidemic in 2016, with up to 50% of the population in Managua infected. With the domesticated Aedes aegypti mosquito as its vector, it is widely assumed that Zika virus transmission occurs within the household and/or via human mobility. We investigated these assumptions by using viral genomes to trace Zika transmission spatially. Methods: We analysed serum samples from 119 paediatric Zika cases participating in the long-standing Paediatric Dengue Cohort Study in Managua, which was expanded to include Zika in 2015. An optimal spanning directed tree was constructed by minimizing the differences in viral sequence diversity composition between patient nodes, where low-frequency variants were used to increase the resolution of the inferred Zika outbreak dynamics. Findings: Out of the 18 houses where pairwise difference in sample collection dates among all the household members was within 30 days, we only found two where viruses from individuals within the same household were up to 10th-most closely linked to each other genetically. We also identified a substantial number of transmission events involving long geographical distances (n=30), as well as potential super-spreading events in the estimated transmission tree. Interpretation: Our finding highlights that community transmission, often involving long geographical distances, played a much more important role in epidemic spread than within-household transmission. Funding: This study was supported by an NUS startup grant (OMS) and grants R01 AI099631 (AB), P01 AI106695 (EH), P01 AI106695-03S1 (FB), and U19 AI118610 (EH) from the US National Institutes of Health.
