Genomic Epidemiology of 2015-2016 Zika Virus Outbreak in Cape Verde

Abstract

During 2015-2016, Cape Verde, an island nation off the coast of West Africa, experienced a Zika virus (ZIKV) outbreak involving 7,580 suspected Zika cases and 18 microcephaly cases. Analysis of the complete genomes of 3 ZIKV isolates from the outbreak indicated the strain was of the Asian (not African) lineage. The Cape Verde ZIKV sequences formed a distinct monophylogenetic group and possessed 1-2 (T659A, I756V) unique amino acid changes in the envelope protein. Phylogeographic and serologic evidence support earlier introduction of this lineage into Cape Verde, possibly from northeast Brazil, between June 2014 and August 2015, suggesting cryptic circulation of the virus before the initial wave of cases were detected in October 2015. These findings underscore the utility of genomic-scale epidemiology for outbreak investigations.

Keywords: Asian lineage; Brazil; Cabo Verde; Cape Verde; West Africa; Zika virus; disease outbreaks; epidemiologic studies; epidemiology; genomics; microcephaly; outbreak; phylogeography; serology; vector-borne infections; viruses.

Figure 1

Locations of suspected Zika cases (dark gray shading), Cape Verde, 2015–2016. Only 2 cases on Boa Vista were confirmed, and those might have been imported.

Figure 2

Suspected Zika cases, cases tested for Zika virus (ZIKV) infection, ZIKV antibody–positive cases, and ZIKV RNA–positive cases, Cape Verde, 2015–2016, by epidemiologic week. A) Cases of suspected ZIKV infection (n = 7,580) (9). B) Cases tested for ZIKV infection, ZIKV antibody–positive cases, and ZIKV RNA–positive cases. Only 1,226 of 7,580 cases of suspected ZIKV infection are included among those tested for ZIKV infection. In addition, some patients with fever only or rash only who did not fit the Zika case definition were also tested for ZIKV infection and included on this graph. ZIKV IgG–positive cases were negative by qRT-PCR and IgM ELISA and confirmed positive for ZIKV IgG by plaque reduction neutralization test. Arrows indicate the time of patient sampling for the 3 sequenced ZIKV isolates (GenBank accession nos. MK241415–7). qRT-PCR, quantitative reverse transcription PCR; –, negative; +, positive.

Figure 3

Maximum clade credibility phylogenetic tree demonstrating migration history of Zika virus (ZIKV) Asian lineage, 2014–2018. A) Phylogeny of 459 ZIKV isolates. The tree base was removed for ease of presentation. Tips of tree are colored according to their sampling location and branches according to their most probable geographic location. Note that sequences from the 2016 Angola outbreak (23) were published during the later stages of preparation of this manuscript and therefore were not included in this Bayesian analysis. Scale bar indicates years. See Appendix Figure 1 for fully annotated tree. B) Expansion of tree containing Cape Verde ZIKV sequences (bold). Clade posterior probabilities are shown at well-supported nodes (>0.9). GenBank accession number, country of origin, and sampling date are provided for each ZIKV sequence.