Genomic surveillance of the Colombian Zika virus outbreak

From the Bedford lab, Vaccine and Infectious Disease Division

During 2015 and 2016, Zika virus (ZIKV) caused a large epidemic in the Americas. There are no vaccines or ZIKV-specific therapeutics for this infection, and disease spread is best contained through understanding ZIKV epidemiology, which informs our understanding of transmission patterns and the populations at risk of contracting the virus. During the 2015-2016 outbreak, Colombia had the second highest ZIKV case load behind Brazil, yet little ZIKV genetic sequence data from Colombia is available, leaving past and present ZIKV transmission dynamics largely undescribed. Although surveillance data was collected during the Americas’ outbreak, it is likely that many cases were missed, making it challenging to detect when Zika began circulating in different countries, as ZIKV most often causes minor disease symptoms. Therefore, surveillance for ZIKV is most accurate when measured with genomic data. To better understand when and how frequently ZIKV was introduced into Colombia, the Bedford group (Vaccine and Infectious Disease Division) recently used available and novel ZIKV sequence data to reconstruct phylogenic trees of ZIKV transmission into and around Colombia. The study, led by Bedford lab members Allison Black and Dr. Louise Moncla, was published in BMC Infectious Diseases.

To first reconstruct general patterns of ZIKV evolution, the authors employed the Bedford lab’s Nextstrain platform to perform phylogenetic analysis. They began by feeding 360 existing Asian-lineage ZIKV sequences sampled from Oceania and the Americas, including Colombia, into their pipeline, which estimates ZIKV evolutionary rates and can be used to infer temporal phylogenies. This analysis corroborated previously published data that found that ZIKV originated in Oceania, and that the Americas outbreak descended from a single introduction into Brazil in late-2013. The authors looked at where Colombia-specific ZIKV samples clustered in the phylogenic tree to see when ZIKV was introduced to Colombia and where those introductions had come from. During the outbreak, the Instituto Nacional de Salud de Colombia and the Universidad del Rosario collected serum samples from individuals with suspected ZIKV infection. For the current study, the authors generated 8 new sequences from these samples. Along with 12 Colombian genomes sequenced by other groups, these sequences cover a broad geographic distribution of Colombia.

When Colombian ZIKV samples were contextualized within the greater ZIKV phylogeny, the authors found that Colombian ZIKV clustered in two distinct clades that each descend from single introductions from Brazil to Colombia. They found that Clade 1, although previously described, entered Colombia in February of 2015, significantly earlier than detection of the first laboratory-confirmed case in September 2015. This suggests that ZIKV circulated undetected for five to eight months. Additionally, the authors found a previously unrecognized second ZIKV clade, highlighting how genomic surveillance can resolve multiple transmission chains that may not be apparent from case surveillance data. Although the authors lacked sufficient intra-Colombia ZIKV samples to reconstruct transmission dynamics within the country, they found evidence for transmission from Colombia onward: Clade 1 viruses spread into bordering countries including Panama, Venezuela, and Peru, while Clade 2 viruses moved into Ecuador. Together, these findings suggest that ZIKV in Colombia arose from two introductions, with most transmission attributable to one of those introductions, and that “the epidemic in Colombia was primarily sustained by transmission within Colombia, rather than by frequent re-introduction by travelers from other countries,” Black explained. “This means that infection prevention measures implemented within Colombia would likely have helped to limit the Colombian epidemic.”

Temporally resolved maximum likelihood trees of 360 ZIKV sequences from Oceania and the Americas.
Temporally resolved maximum likelihood trees of 360 ZIKV sequences from Oceania and the Americas. Figure provided by Allison Black.

This study improved genetic sampling for ZIKV in the Americas by contributing to public sequence data and performing a detailed genomic epidemiologic analysis for Colombia’s outbreak finding that most of Colombia’s ZIKV transmission resulted from local transmission within the country. Knowing what type of transmission pattern drove the outbreak informs how an outbreak is best contained. Black said she wants to understand "what factors facilitated Zika dispersal within Colombia.” These findings, in addition to retrospectively elucidating what facilitated ZIKV transmission in Colombia, could also inform surveillance and prevention for future epidemics, she explained. “I think if we could investigate that question it would really enhance our understanding of arboviral disease dynamics more generally, and perhaps help us limit transmission more effectively when we have another outbreak of a mosquito-borne virus.”

This work was supported by the National Science Foundation, the National Institutes of Health, the Life Sciences Research Foundation, the Open Philanthropy Project, Grupo de Virología, Dirección de Redes en Salud Pública, Instituto Nacional de Salud, Bogotá D.C, Colombia, the Gobernación de Córdoba, sistema general de regalias (SGR) Colombia, and the Dirección de Investigación e Innovación from Universidad del Rosario.

UW/Fred Hutch Cancer Consortium member Elizabeth Halloran contributed to this work.

Black A, Moncla LH, Laiton-Donato K, Potter B, Pardo L, Rico A, Tovar C, Rojas DP, Longini IM, Halloran ME, Peláez-Carvajal D, Ramírez JD, Mercado-Reyes M, Bedford T. 2019. Genomic epidemiology supports multiple introductions and cryptic transmission of Zika virus in Colombia. BMC Infectious Diseases.  2019 Nov 12;19(1):963. doi: 10.1186/s12879-019-4566-2.