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Paola Clemente, the woman who died of fatigue for a few euros in Italy. February 2011 and November 2013. Virus abbreviations: YFV, yellow fever virus; SLEV, St. IgG from previous flavivirus exposures than from the most recent infection. ZIKV and DENV infections. DENV infection preceded each clinical disease examined with sera from secondary infections. We declare that we have no competing interests. PAGE and stained with Coomassie blue to determine the relative amounts of viral proteins in each preparation. MFI originating from microarrayed antigens and i is the infecting virus species.

IgG and IgM were increasing in tandem with virus replication. Received 8 February 2017. Accepted manuscript posted online 22 February 2017. AS, ZIKV from Asia; JEV, Japanese encephalitis virus; ROCV, Rocio virus. Zika disease epidemic and to future outbreaks. Microarrays of flavivirus antigens. The final SVM model was generated using the optimal parameters with complete training data sets. Animal and human sera. New England BioLabs Inc.

DENV and ZIKV isolates. Data acquisition and analysis. DENV and ZIKV infections. The E proteins of ZIKV and DENV have a high degree of structural similarity that may contribute to shared antibody epitopes. Zika virus infections in environments of flavivirus endemicity. Quantitative comparisons of antibodies directed to the infecting virus versus all other flaviviruses.

Blood samples were obtained using a Vacutainer system or needle and syringe from the femoral or saphenous vein. Overlap in rising and waning antibody responses to independent infections. RNA is typically no longer detected. Integrated DNA Technologies, Inc. Blosum62 as the protein weight matrix, and all other options left as default. Specificity and kinetics of the humoral immune response to ZIKV. The extent of disease enhancement in human ZIKV infections due to preexisting flavivirus antibodies is not well documented.

Antibody specificity of primary and secondary flavivirus infections. All authors reviewed and edited the manuscript. Differentiation of nonhuman primates challenged with ZIKV or DENV by specific IgG binding to E antigens. National Institutes of Health. Table 1 and Fig. Sera were identified as WNV positive by nucleic acid testing, indicating a current WNV infection at the time of blood donation.

Accepted 18 February 2017. Antibody responses to ZIKV. NHPs essentially bound only to ZIKV E antigens. Zika disease and previous infections. Table 1; see Fig. ZIKV infection and offer considerations for development of vaccines and diagnostics. Connor DH, Ulrich RG. PCR during the acute phase of infection. Zika virus antibodies that will vary with time from infections.

However, results from some in vitro assays will be difficult to extrapolate to human cases. Naval Medical Research Unit No. Controlling mosquitos to prevent disease is a consummate goal of public health authorities. Currently CDC recommends testing pregnant women who have traveled to endemic countries, whether or not they experience symptoms of ZIKV. Are enhanced domestic public health responses, including aggressive mosquito control efforts, warranted despite potential risks from public exposure to vector control agents? South and Latin Americas in 2015 through global migration of mosquitoes and human travel patterns escalates this threat to emergency levels. Some issues will be clarified as public health authorities and medical providers learn more. They include purely voluntary recommendations, mandatory measures that set conditions on testing, and compulsory interventions.

Current efforts focused on development of a vaccine are still months from fruition, and thus of little consequence to tens of millions currently at risk of infection. State and federal water laws may require spray permits or environmental impact assessments, subject to waiver under appropriate emergency declarations. In such cases, laws in many jurisdictions allow public health officials to classify private property as a public health nuisance to require mosquito abatement actions by owners. January 2016 to provide information and resources for eliminating breeding grounds from homes and properties. Dan Hanfling, MD, is a Contributing Scholar at the UPMC Center for Health Security and Clinical Professor of Emergency Medicine, George Washington University School of Medicine. As discussed below, difficult choices at the intersection of public health, medical and legal triage must be made amidst present and future uncertainties about the trajectory and morbidity of ZIKV among specific populations. Originally discovered in Uganda in 1947, ZIKV, like Ebola, was largely dormant for decades.

In 2015, California legislated away existing vaccine exceptions for religious and philosophical exemptions. Finding and killing Aedes mosquitoes are not not difficult. ZIKV are thought currently to extend mostly to vulnerable infants and pregnant women. Compliance with legal pesticide requirements, use of integrated pest management and proper training of pesticide applicators can minimize risks and liabilities. ZIKV, but these conditions can only be detected well after birth when cognitive testing can be conducted. Connor College of Law, ASU. Mandatory newborn screening for a multiple condition is common practice in the US. ZIKV is yet another example of an emerging infectious disease with public health consequences exceeding the normal provision of medical care. Dengue fever and Yellow fever vaccine, commonly recommended for travelers to areas where ZIKV is currently endemic.

Contrast a voluntary approach to mandatory testing of infants. Several companies are working to develop rapid, not difficult and accurate tests for ZIKV as existing blood tests are problematic. The US National Security Council has directed federal agencies to plan for the emerging virus. Testing recommendations are problematic. Public health legal powers to test and screen individuals and populations vary. Still, even voluntary testing can implicate difficult policy choices. With conditions like ZIKV, where medical and public health findings are constantly evolving, the practice of medical and legal triage intersect, as illustrated below. Most of these practitioners have limited experience with preparing for public health emergencies, implementing crisis standards of care and reporting ZIKV cases.

Many of the nations experiencing widespread ZIKV infections have religious foundations and related laws that deeply conflict with these services. ZIKV is projected to infect multiple millions globally before this current wave crests. As new data arise, key decisions in medical and legal triage for the management of this emerging infectious threat must be made in unison based on best medical and legal practices leading to improved health outcomes. Public health and medical limitations are compounded by a potential lack of preparedness, as seen with initial cases of EVD in the US. So long as the spread of ZIKV continues to be dominated by mosquitos, and not people, travel restrictions or bans lack utility, carry significant economic impacts and potentially infringe human rights. For example, government recommendations for voluntary ZIKV testing of adult pregnant women are lawful even if test results are somewhat unreliable. CDC has issued voluntary travel warnings for pregnant women and others in affected countries.

Zika may not generate the same fears as Ebola, but it does present other, complex social challenges. President Obama presented a supplemental budget to Congress recently focused on improving diagnosis, developing medical countermeasures and coordinating preparedness and response strategies. Microcephaly, in which babies are born with abnormally small heads and brains, has been associated with corresponding increases in rates of fetal demise and moderate to severe developmental delays in the offspring of women infected with ZIKV. That is, until suggestions about the potential adverse effects of the vaccine arise, whether based in fact or fiction. ZIKV in the US. GBS or other conditions materialize? Its transfer to fetuses through pregnant women, however, can have catastrophic consequences. Finally, while domestic testing demands are being met now, rapidly and accurately testing thousands of at risk pregnant women will be difficult if ZIKV transmission spreads across southern states later this spring. Pervasive mistruths about current childhood vaccine safety continue to hamper vaccination rates in specific subpopulations in the US. What is legally authorized depends on what is justified from a public health or medical perspective.

Concerned about discrimination and trade, WHO has expressed disdain for any national travel bans or restrictions. Public health challenges of ZIKV extend from risks primarily to unborn children. Conversely, if efficacious treatments for ZIKV infections among infants become a part of the standard of care, failures to screen at risk infants may lead to liability later if their disabilities could have been prevented. The mere specter of adverse events related to ZIKV vaccines may obviate their use, changing the nature of how they are allocated. Typical fumigation of communities may not fully address their spread. Vision and hearing problems among newborns have also emerged as potential ZIKV complications. How many resources should be expended to test asymptomatic travelers and those living in endemic areas when current data are insufficient to accurately assess risk to a pregnancy from the disease? There is no specific treatment for ZIKV.

When and how often infection in the course of pregnancy may lead to such disabilities are uncertain. This article was prepared for publication by Marisa Pereira Rodrigues, an Assistant Editor for JURIST Commentary. Furthermore, mandatorily screening infants for ZIKV at birth may be questionable if there are no proven interventions to address their potential medical complications. Initial answers via legal triage can change immediately via declared states of emergency, disaster, or public health emergency, as in Florida, Puerto Rico and Hawaii. Unlike with EVD, ZIKV is spread primarily via the Aedes species of mosquitos. Still, Brazilian authorities recommended that people avoid kissing to prevent infection during the February 2016 Carnival. Multiple countries, including Brazil, Honduras and Mexico, have made similar declarations.

So long as the testing is truly voluntary a patient may choose whether to participate or not via informed consent. Adding ZIKV to the list of newborn conditions tested may seem pragmatic, but could still lead to legal questions. Not everyone may be able or willing to assist in mosquito abatement efforts. CDC recommends source reduction and larvicide treatments early in the breeding season, and adulticide treatments only after local ZIKV cases are detected. The 2016 Summer Olympics in Brazil and continued mosquito migrations to North America heighten the potential for rapid global spread of ZIKV. ZIKV, its symptoms and morbidity among the clinical community. Who gets available vaccines first?

Are suggested restrictions on pregnancy in El Salvador, Colombia, Ecuador and Jamaica warranted given their significant impacts on reproductive rights, economic interests and social status? Hick, MD, is a Professor of Emergency Medicine at the University of Minnesota School of Medicine and an Emergency Physician at Hennepin County Medical Center. Recently, federal legislators objected to the potential for federal ZIKV preparedness funds to support women who may choose abortions if faced with positive ZIKV test results. How limited resources are distributed is ethically perplexing, especially given intersecting shifts in medical data and legal responsibilities. Even if a safe vaccine can be developed, initial supplies will be limited. As a result, community education on mosquito source reduction is integral. None of these other routes is known presently to be the source of major, or even minor, outbreaks. One of the most difficult issues in the context of emerging infectious disease outbreak is how to allocate available limited resources, particularly medical countermeasures.

Profound reproductive rights issues surround access and use of contraception and abortion, especially among pregnant minors. Who needs doctors at all if care is reduced to point and click? Trade Binary Option In Canada Illegal Binary Option Trading Guide Who needs doctors at all if care is reduced to point and click? Top Five Successful Strategies. Early ultrasounds may not detect microcephaly in mothers with Zika amava. In fact, the only region outside Florida with local ZIKV transmission is southern Texas 27, which is also the only other region with recent DENV outbreaks 19, 20, 21. Determining the sources and routes of ZIKV introductions could help to mitigate future outbreaks. Return of epidemic dengue in the United States: implications for the public health practitioner. On the seasonal occurrence and abundance of the Zika virus vector mosquito Aedes aegypti in the contiguous United States. June 2016, by method of travel.

Increasing dengue incidence in Singapore over the past 40 years: population growth, climate and mobility. The number of ZIKV cases reported by each country are likely to be underestimates, in part because the majority of ZIKV infections are asymptomatic 2, 31. Gross for designing and providing enrichment probes. Vertical dashed lines show the inferred mean persistence time for lineages F1, F2 and B based on their tMRCAs. Zika virus: new clinical syndromes and its emergence in the Western hemisphere. All authors read and approved the manuscript. The number of travellers and reported ZIKV incidence rate for the country or territory of origin were used to estimate the proportion of infected travellers coming from each region with ZIKV in the Americas. Florida DOH because this research was performed with leftover clinical diagnostic samples involving no more than minimal risk.

Given that the majority of ZIKV infections are asymptomatic 2, 31, the true number of ZIKV cases is likely to have been much higher. Samtools was used to sort the aligned BAM files and to generate alignment statistics 47. Country and territory total population sizes to calculate weekly and monthly ZIKV incidence rates were also obtained from PAHO 74. The probes were designed to cover the entire ZIKV genome and to encompass the genetic diversity present on GenBank on 14 January 2016. First detection of natural infection of Aedes aegypti with Zika virus in Brazil and throughout South America. Improving marginal likelihood estimation for Bayesian phylogenetic model selection. Up to 50 mosquitoes of the same species and sex were pooled per trap. Differential susceptibilities of Aedes aegypti and Aedes albopictus from the Americas to Zika virus. Zika virus evolution and spread in the Americas.

Cruise ship itineraries and occupancy rates. Outbreak of Zika virus infection, Chiapas State, Mexico, 2015, and first confirmed transmission by Aedes aegypti mosquitoes in the Americas. Clade posterior probabilities are indicated by white circles filled with black relative to the level of support. We investigated ZIKV infection rates and travel patterns to corroborate our phylogenetic evidence for Caribbean introductions. Together, these findings suggest that a high incidence of ZIKV in the Caribbean, combined with frequent travel, could have played a key role in the establishment of ZIKV transmission in Florida. This is similar to infection rates during DENV and CHIKV outbreaks 23. Dade County for different R 0 values. Origin of the dengue virus outbreak in Martin County, Florida, USA 2013. ZIKV transmission entering major US airports from October 2014 to September 2015, which we used to assess the potential for ZIKV introductions outside of Florida.

MAFFT 53 and inspected manually. The one local ZIKV infection diagnosed in Duval County was believed to have originated elsewhere in Florida. Our study provides an understanding of how ZIKV initiates transmission in new regions. Zika virus genomes from Pacific islands and the epidemic in the Americas. The dates of the introductions could be more recent if multiple F1 or F2 lineage viruses arrived independently. The probability of ZIKV persistence after introduction for different R 0 values. There was also one case of unknown origin. The content of this publication does not necessarily reflect the views or policies of the US Army, the Department of Health and Human Services, the CDC, or the Florida Department of Health.

Cruise and flight traffic entering Miami from regions with Zika virus transmission. PCR bias and decreased coverage depth. The best fit model was a relaxed molecular clock along with a Bayesian Skyline model 63. Big city, small world: density, contact rates, and transmission of dengue across Pakistan. ZIKV transmission in Miami. ZIKV cases in 2016. However, more than two introductions would be necessary to substantially change our estimates for the timing of the earliest introduction.

Similarly, even though we found that the Florida ZIKV genomes clustered together with sequences from the Dominican Republic, our results do not prove that ZIKV entered Florida from this country. June to November 2016, 99. Because of severe undersampling of ZIKV genomes, however, we cannot rule out other source areas. Identification of dengue fever cases in Houston, Texas, with evidence of autochthonous transmission between 2003 and 2005. US cities presented in Extended Data Fig. Zika virus in Europe. Estimating the transmission potential of supercritical processes based on the final size distribution of minor outbreaks. Clinical samples from locally acquired ZIKV infections were collected between 22 June and 11 October 2016. For the following, we took a forward simulation approach, drawing random samples from this distribution. ZIKV sequencing at USAMRIID was performed using a targeted enrichment approach.

Zika virus infections in childbearing women in the Americas. All other data are available in the Extended Data or Supplementary Information, or upon request. Weekly reported Zika virus case numbers and incidence rates in the Americas. The software and basemaps are open source and freely available to anyone. ZIKV genomes sequenced from outbreaks in the Pacific islands and the epidemic in the Americas. Trimmomatic: a flexible trimmer for Illumina sequence data. Estimating the subcritical transmissibility of the Zika outbreak in the State of Florida, USA, 2016. ZIKV is vectored primarily by Aedes mosquitoes 10, 11, 12, 13. All contributions are listed in order of authorship. HPD intervals are shown for the tMRCAs.

Human Research Protection Program. Reported ZIKV cases per country or territory from January to June 2016, normalized by total population. Americas 14 has facilitated the establishment of DENV, CHIKV, and now probably ZIKV as endemic in this region 15. ZIKV case numbers for Florida were obtained from the Florida DOH. Additionally, as a sensitivity analysis we modelled a preferential sampling process in which larger clusters are more likely to be drawn from than smaller clusters. Therefore we used WebPlotDigitizer v3. Assuming that they represent two independent introductions, we estimated when each of these lineages arrived in Florida. The global distribution of the arbovirus vectors Aedes aegypti and Ae. Tips are coloured according to collection location. All published and available complete ZIKV genomes of the Asian genotype from the Pacific and the Americas were retrieved from GenBank public database in December 2016. These findings, however, do not indicate that cruise ships themselves are risk factors for human ZIKV infection, but only that they served as a major mode of transportation from areas with active transmission. Our analyses show that most introductions were linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area.

Therefore, we expect that outbreaks in Florida will cycle with ZIKV transmission dynamics in the Americas 7, 8, 15. Simulating normalizing constants: from importance sampling to bridge sampling to path sampling. To investigate whether the transmission of ZIKV in Florida coincided with travel patterns from ZIKV endemic regions, we obtained the number of passengers arriving at airports in Florida via commercial air travel. While the air traffic was based on the reported number of travellers, we estimated the sea traffic by ship capacity. Maximum likelihood phylogenetic estimation from DNA sequences with variable rates over sites: approximate methods. ZIKV activities timelines published by the Florida DOH 34. ZIKV diagnosed in Florida. Despite this, we estimated that the average R 0 was less than 1 and therefore multiple introductions were necessary to give rise to the observed outbreak 32. All ZIKV sequencing data are available under NCBI BioProjects PRJNA342539 and PRJNA356429. Countering the Zika epidemic in Latin America. These findings suggest that ZIKV moved among areas of Miami. We contacted PAHO multiple times with the hope of gaining access to the raw data included in the bar graphs, but our requests were unfortunately denied.

Port of Miami and reported ship schedules from www. Individual sample GenBank access numbers are listed in Supplementary Table 1a. This distribution L is plotted in Extended Data Fig. Pacific region: a modelling study. ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. Quality control and preprocessing of metagenomic datasets. ZikaAsian V1 scheme, as described 24. The random hexamer associated with read one and the Illumina adaptors were removed from the sequencing reads using Cutadapt v1. Office of Human Use and Ethics. Vector competence of American mosquitoes for three strains of Zika virus. Persistence is measured as the number of days from initial introduction of viral lineages until their extinction.

PCR and antibody tests following interim guidelines 3, 37, 38, 39. Zika virus: diagnostics for an emerging pandemic threat. Zika virus and complications. Ministry of Public Health, Ecuador. In most cases, the weekly case numbers per country were reported only in bar graphs. CDC Cooperative Agreement U01CK000510. Greater early season potential for Zika virus introductions into Miami. Snakemake was used as the workflow management system 48. Dual indexing, with no overlapping indices, was used. ZIKV amplicons on the MiSeq. Pew Biomedical Scholar, and is supported by NIH NCATS CTSA UL1TR001114, NIAID contract HHSN272201400048C, and The Ray Thomas Foundation.

Times to key events in the course of Zika infection and their implications: a systematic review and pooled analysis. Zika virus case counts in the US. UTR, C, prM, M, E, NS1, and NS2 regions. Florida DOH investigation process were obtained from the ZIKV resource website 34 and daily updates 35. Scheduled cruise ship capacities were extracted from www. By analysing surveillance and genetic data, we show that ZIKV moved among transmission zones in Miami. Mahan Postdoctoral Fellowship from the Computational Biology Program at Fred Hutch. Key West, Florida, USA, 2010. First US case of Zika virus infection is identified in Texas.

Molecular clock dating of Zika virus clades. ZIKV genomes add to the Caribbean dataset, but do not directly influence our conclusions about the source of ZIKV introductions into Florida. Lineage F4 contains two identical ZIKV genomes from the same patient. These findings suggest that whereas ZIKV outbreaks occurred throughout the Americas, the Caribbean islands were the main source of local ZIKV transmission in Florida. ML inference by jModelTest2 56. Superspreading and the effect of individual variation on disease emergence. Measuring the path toward malaria elimination.

Dengue in Puerto Rico. ZIKV transmission 32, the potential for future ZIKV outbreaks in this region is dependent upon activity elsewhere. Zika virus outbreak on Yap Island, Federated States of Micronesia. Matplotlib: A 2D graphics environment. ZIKV introductions also contributed to the outbreak. RNA from the amplicon and enrichment approaches, respectively.

Amplification was performed following conditions as previously described 44. The parameter k represents the variation in the number of secondary cases generated by each case of ZIKV 64. The reagent FuPa was used to digest the modified primer sequences after amplification.