Summary During mammalian pregnancy, the placenta acts as a barrier between the maternal and fetal compartments. The recently observed association between Zika virus (ZIKV) infection during human pregnancy and fetal microcephaly and other anomalies suggests that ZIKV may bypass the placenta to reach the fetus. This led us to investigate ZIKV infection of primary human trophoblasts (PHT), which are the barrier cells of the placenta. We discovered that PHT cells from full-term placentas are refractory to ZIKV infection. In addition, medium from uninfected PHT cells protects non-placental cells from ZIKV infection. PHT cells constitutively release the type III interferon (IFN) IFNλ1, which functions in both a paracrine and autocrine manner to protect trophoblast and non-trophoblast cells from ZIKV infection. Our data suggests that for ZIKV to access the fetal compartment, it must evade restriction by trophoblast-derived IFNλ1 and other trophoblast-specific antiviral factors and/or use alternative strategies to cross the placental barrier.

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.

Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations.

SummaryBackground The microcephaly epidemic, which started in Brazil in 2015, was declared a Public Health Emergency of International Concern by WHO in 2016. We report the preliminary results of a case-control study investigating the association between microcephaly and Zika virus infection during pregnancy.

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The clinical outcomes associated with Zika virus (ZIKV) in the Americas have been well documented, but other aspects of the pandemic, such as attack rates and risk factors, are poorly understood. We prospectively followed a cohort of 1453 urban residents in Salvador, Brazil, and, using an assay that measured immunoglobulin G3 (IgG3) responses against ZIKV NS1 antigen, we estimated that 73% of individuals were infected during the 2015 outbreak. Attack rates were spatially heterogeneous, varying by a factor of 3 within a community spanning 0.17 square kilometers. Preexisting high antibody titers to dengue virus were associated with reduced risk of ZIKV infection and symptoms. The landscape of ZIKV immunity that now exists may affect the risk for future transmission.

Affected nations need to prepare to provide complex and costly multidisciplinary care that children diagnosed with this new congenital syndrome will require.

Brazil currently accounts for the majority of dengue cases reported in the Americas, with co-circulation of DENV 1, 2 and 3. Striking variation in the epidemiological pattern of infection within cities has been observed. Therefore, investigation of dengue transmission in small areas is important to formulate control strategies. A population-based household survey was performed in three diverse socio-economic and environmental areas of Recife, a large urban center of Brazil, between 2005 and 2006. Dengue serostatus and individual- and household-level risk factors for infection were collected in residents aged between 5 and 64 years. A total of 2,833 individuals were examined, and their residences were geo-referenced. Anti-dengue IgG antibodies were measured using commercial ELISA. The dengue seroprevalence and the force of infection were estimated in each area. Individual and household variables associated with seropositivity were assessed by multilevel models for each area. A spatial analysis was conducted to identify risk gradients of dengue seropositivity using generalized additive models (GAM). The dengue seroprevalence was 91.1%, 87.4% 74.3%, respectively, in the deprived, intermediate and high socioeconomic areas, inversely related to their socio-economic status. In the deprived area, 59% of children had already been exposed to dengue virus by the age of 5 years and the estimated force of infection was three times higher than that in the privileged area. The risk of infection increased with age in the three areas. Working or studying outside the home area was a risk factor for seropositivity in the deprived area (OR=2.26; 95% CI: 1.18-4.30). Number of persons per room was a risk factor for seropositivity in the intermediate (OR=3.00; 95% CI: 3.21-7.37) and privileged areas (OR=1.81; 95% CI: 1.07-3.04). Living in a house, as opposed to an apartment, was a risk factor for seropositivity in the privileged area (OR=3.62; 95% CI: 2.43-5.41). The main difference between the privileged and other areas could be attributed to the much larger proportion of apartment dwellers. Intensive vector control, surveillance and community education should be considered in deprived urban areas where a high proportion of children are infected by an early age.