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      Zika Virus Outbreak in Haiti in 2014: Molecular and Clinical Data

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          Abstract

          Background

          Zika virus (ZIKV), first isolated in Uganda in 1947, is currently spreading rapidly through South America and the Caribbean. In Brazil, infection has been linked with microcephaly and other serious complications, leading to declaration of a public health emergency of international concern; however, there currently are only limited data on the virus (and its possible sources and manifestations) in the Caribbean.

          Methods

          From May, 2014-February, 2015, in conjunction with studies of chikungunya (CHIKV) and dengue (DENV) virus infections, blood samples were collected from children in the Gressier/Leogane region of Haiti who presented to a school clinic with undifferentiated febrile illness. Samples were initially screened by RT-PCR for CHIKV and DENV, with samples negative in these assays further screened by viral culture.

          Findings

          Of 177 samples screened, three were positive for ZIKV, confirmed by viral sequencing; DENV-1 was also identified in culture from one of the three positive case patients. Patients were from two different schools and 3 different towns, with all three cases occurring within a single week, consistent with the occurrence of an outbreak in the region. Phylogenetic analysis of known full genome viral sequences demonstrated a close relationship with ZIKV from Brazil; additional analysis of the NS5 gene, for which more sequences are currently available, showed the Haitian strains clustering within a monophyletic clade distinct from Brazilian, Puerto Rican and Guatemalan sequences, with all part of a larger clade including isolates from Easter Island. Phylogeography also clarified that at least three major African sub-lineages exist, and confirmed that the South American epidemic is most likely to have originated from an initial ZIKV introduction from French Polynesia into Easter Island, and then to the remainder of the Americas.

          Conclusions

          ZIKV epidemics in South America, as well as in Africa, show complex dissemination patterns. The virus appears to have been circulating in Haiti prior to the first reported cases in Brazil. Factors contributing to transmission and the possible linkage of this early Haitian outbreak with microcephaly remain to be determined.

          Author Summary

          Zika virus is currently spreading rapidly through the Americas, including the Caribbean, where it has emerged as a major public health problem due to the linkage with birth defects, including microcephaly. We report the isolation of Zika virus from 3 children in rural Haiti in December, 2014, as part of a study of acute undifferentiated febrile illness that was being conducted by our research group; from one of these children, we also isolated dengue virus serotype 1. On analysis of nucleotide sequence data from these and Zika strains from other locales, the South American/Haitian sequences cluster within the Asian clade and clearly branch out from a sequence circulating in Easter Island, which originated, in turn, from French Polynesia. On further analysis of one specific gene sequence for which more data were available, there appeared to be slight separation of Haitian strains and the strains from Brazil, Suriname, Puerto Rico and Guatemala, with molecular clock analysis suggesting that Zika virus was present in Haiti as early as mid-2013. These findings raise questions about the origin of Zika virus in the Caribbean, and subsequent patterns of circulation of the virus within the Americas.

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          Most cited references7

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          Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth.

          The suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infects human neural progenitor cells (hNPCs) derived from induced pluripotent stem cells. Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth. Global gene expression analysis of infected hNPCs reveals transcriptional dysregulation, notably of cell-cycle-related pathways. Our results identify hNPCs as a direct ZIKV target. In addition, we establish a tractable experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds.
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            Zika virus: following the path of dengue and chikungunya?

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              • Article: not found

              Cumulative live-birth rates after in vitro fertilization.

              Outcomes of in vitro fertilization (IVF) treatment are traditionally reported as pregnancies per IVF cycle. However, a couple's primary concern is the chance of a live birth over an entire treatment course. We estimated cumulative live-birth rates among patients undergoing their first fresh-embryo, nondonor IVF cycle between 2000 and 2005 at one large center. Couples were followed until either discontinuation of treatment or delivery of a live-born infant. Analyses were stratified according to maternal age and performed with the use of both optimistic and conservative methods. Optimistic methods assumed that patients who did not return for subsequent IVF cycles would have the same chance of a pregnancy resulting in a live birth as patients who continued treatment; conservative methods assumed no live births among patients who did not return. Among 6164 patients undergoing 14,248 cycles, the cumulative live-birth rate after 6 cycles was 72% (95% confidence interval [CI], 70 to 74) with the optimistic analysis and 51% (95% CI, 49 to 52) with the conservative analysis. Among patients who were younger than 35 years of age, the corresponding rates after six cycles were 86% (95% CI, 83 to 88) and 65% (95% CI, 64 to 67). Among patients who were 40 years of age or older, the corresponding rates were 42% (95% CI, 37 to 47) and 23% (95% CI, 21 to 25). The cumulative live-birth rate decreased with increasing age, and the age-stratified curves ( or = 40 years) were significantly different from one another (P<0.001). Our results indicate that IVF may largely overcome infertility in younger women, but it does not reverse the age-dependent decline in fertility. 2009 Massachusetts Medical Society
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                25 April 2016
                April 2016
                : 10
                : 4
                : e0004687
                Affiliations
                [1 ]Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America
                [2 ]Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, United States of America
                [3 ]Department of Health Services Research, Management, and Policy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, United States of America
                [4 ]Christianville Foundation School Clinic, Gressier, Haiti
                [5 ]Department of Pathology, Immunology, and Laboratory Sciences, College of Medicine, University of Florida, Gainesville, Florida, United States of America
                [6 ]Department of Infectious Parasitic and Immunomediated Diseases, Reference Centre on Phylogeny, Molecular Epidemiology and Microbial Evolution (FEMEM)/Epidemiology Unit, Istituto Superiore di Sanita, Rome, Italy
                [7 ]Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America
                RTI International, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JLe VMBDR BO MS JGM. Performed the experiments: JLe MEB MR JLo. Analyzed the data: JLe JGM MS EC MC. Wrote the paper: JLe VMBDR BO MS JGM MEB MR JLo TT SC GA EC MC. Clinical patient management and data collection: TT SC GA. Had full access to all data and had final responsibility for the decision to submit for publication: JGM.

                Article
                PNTD-D-16-00366
                10.1371/journal.pntd.0004687
                4844159
                27111294
                ecb0f662-4f15-488a-a84e-060d835d66ed
                © 2016 Lednicky et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 March 2016
                : 13 April 2016
                Page count
                Figures: 4, Tables: 0, Pages: 11
                Funding
                The authors received no funding outside of the University of Florida for the work described. Funding was from an internal University of Florida pilot grant fund. Funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Sequence data is available in GenBank (accession number KU509998).

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