Epidemic establishment and cryptic transmission of Zika virus in Brazil and the Americas

Abstract

Previous phylogenetic analyses indicated that the ZIKV epidemic was caused by the introduction of a single Asian genotype lineage into the Americas around late 2013, at least one year before its detection there 4 . An estimated 100 million people in the Americas are predicted to be at risk of acquiring ZIKV once the epidemic has reached its full extent 5 . However, little is known about the genetic diversity and transmission history of the virus in different regions in Brazil 6 . Reconstructing ZIKV spread from case reports alone is challenging because symptoms (typically fever, headache, joint pain, rashes, and conjunctivitis) overlap with those caused by co-circulating arthropod-borne viruses 7 and due to a lack of nationwide ZIKV-specific surveillance in Brazil before 2016. [Figure 1 around here]To address this we undertook a collaborative investigation of ZIKV molecular epidemiology in Brazil, including results from a mobile genomics laboratory that travelled through NE Brazil during June 2016 (the ZiBRA project; http://www.zibraproject.org). Of five regions of Brazil (Fig. 1a), the Northeast region (NE Brazil) has the most notified ZIKV cases (40% of Brazilian cases) and the most confirmed microcephaly cases (76% of Brazilian cases, to 31 Dec 2016 2 ), raising questions about why the region has been so severely affected 8 . Further, NE Brazil is the most populous region of Brazil with the potential for year-round ZIKV transmission 9 . With the support of the Brazilian Ministry of Health and other institutions (Acknowledgements), the ZiBRA lab screened 1330 samples (almost exclusively serum or blood) from patients residing in 82 municipalities across five federal states in NE Brazil ( Fig. 1 On average, ZIKV viremia persists for 10 days after infection; symptoms develop ~6 days after infection and can last 1-2 weeks 10 . In line with previous observations in Colombia 11 , we found that the RT-qPCR+ samples in NE Brazil were, on average, collected only two days after onset of symptoms. The median RT-qPCR cycle threshold (Ct) value of positive samples was correspondingly high, at 36 (Extended Data Fig. 1). For NE Brazil, the time series of RT-qPCR+ cases was positively correlated with the number of weekly-notified cases (Pearson's ρ=0.62; Fig. 1b).The ability of the mosquito vector Aedes aegypti to transmit ZIKV is determined by ecological factors that affect adult survival, viral replication, and infective periods 12 .To investigate the receptivity of each Brazilian region to ZIKV transmission, we used a measure of vector climatic suitability derived from monthly temperature, relative humidity, and precipitation data 9 . Using linear regression we find that, for each Brazilian region, there is a strong association between estimated climatic suitability and weekly notified cases (Figs. 1b,1c; adjusted R 2 >0.84, P<0.001; Extended Data Table 2). Similar to previous findings obtained for dengue virus outbreaks 13,14 , notified ZIKV cases lag climatic suitability by ~4 to 6 weeks in all regions, except NE Brazil,...

The phylogenomics of evolving virus virulence

“…We show that virus phylogenies are being increasingly used to help identify virulence determinants and that the data obtained can be used to test general theories of virulence evolution. Such a phylogenomic approach to studying virulence evolution is timely because of the rapidity with which virus genome sequence data are now being generated, including during ongoing disease outbreaks of emerging viruses [19][20][21] , and because of the development of new phylogeny-based methods for studying and visualizing genomic data [22][23][24] . However, the success of this approach also requires that phylogenomic data are combined with relevant clinical, epidemiological and experimental metadata so that a direct link can be made between virulence, virus genotype and phenotype, and population fitness.…”

“…120 ), and those cases from the Americas, particularly Brazil, were linked to more severe diseases, including congenital abnormalities such as microcephaly 121 . Phylogenetic analysis revealed that the most recent Zika epidemics are due to the Asian lineage of ZIKV, rather than the African lineage 122 , and that the virus spread cryptically in Brazil for at least a year before its detection 20 . Although there are multiple amino acid differences between the African and Asian lineages 122,123 , it has been claimed that those in the Asian lineage that spread through the Americas may be directly linked to both increased infectivity in Aedes aegypti mosquitoes 124 and microcephaly, most notably a Ser139Asn (S139N) amino acid change in the PrM protein 125 .…”

Nextstrain: real-time tracking of pathogen evolution

“…The regularly updated nature and rapidity of these analyses is crucial to the monitoring and understanding of pathogen epidemiology and evolution. Sequencing times and costs are continually dropping, with on-the-ground sequencing being deployed during the recent West African Ebola and Zika epidemics [2,3]. However, this speed of sequencing must be complemented with rapid methods by which to analyse, interpret, and disseminate results.…”

Genome sequencing reveals Zika virus diversity and spread in the Americas

“…The number of ZIKV genomes publicly available prior to this study is the result of an NCBI GenBank 35 search for ZIKV in February 2017. We filtered any sequences with length <4000 nt, excluded sequences that are being published as part of this study or a companion paper 10,11 , excluded sequences from non-human hosts, and excluded sequences labeled as having been passaged. We counted fewer than 100 sequences, the precise number depending on details of the count.…”