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AgendaHearing to review emerging health threats and the Zika supplemental request WitnessesThomas R. Frieden, M.D.DirectorCenters for Disease Control and Prevention Anthony Fauci, M.D.DirectorNational Institute of Allergy and Infectious Diseases

Labor, Health and Human Services, and Education: Hearing on Emerging Health Threats and the Zika Supplemental Funding Requesthttp://www.appropriations.senate.gov/hearings/labor-health-and-human-services-and-education-hearing-on-emerging-health-threats-and-the-zika-supplemental-funding-request Date: Thursday, February 11, 2016Add to my CalendarTime: 10:00 AMLocation: Dirksen Senate Office Building 138

Zika virus has been discovered in the placentas of at least three American women who contracted the virus while traveling and miscarried after their return to the United States, the chief pathologist at the Centers for Disease Control and Prevention told STAT on Wednesday. The finding adds to a growing mound of evidence that Zika infection during pregnancy can pass from the mother to the fetus she carries. It is believed that in some such cases, the virus attacks the developing brain, triggeringmicrocephaly, a condition in which newborns have abnormally small heads. There have already been reports, from the United States and Brazil, of traces of Zika virus being found in amniotic fluid and placentas from women who were discovered to be carrying fetuses with microcephaly. Read more: Obama seeks $1.8 billion to fight Zika virusAnd last month the CDC reported it had found the virus in brain tissues from two microcephalic infants from Brazil who died shortly after birth. Those findings, initially reported via the media, were published Wednesday in CDC’s in-house journal Morbidity and Mortality Weekly Report. Also on Wednesday, researchers from Slovenia reported a supporting finding in the New England Journal of Medicine. Together, the new reports lend additional weight to the recommendationsfrom public health authorities at the CDC and elsewhere that women who are pregnant should avoid traveling to places where Zika virus is spreading. Health officials have speculated that infection in pregnancy can also lead to an increased rate of miscarriages. The United States has not previously reported miscarriages in American travelers who have contracted the virus, but Dr. Sherif Zaki, the CDC’s chief pathologist, said the agency was now aware of at least three such cases. He said they miscarried early in their pregnancies but did not say where the women lived. The Slovenian team that found Zika in brain tissue, from the University of Ljubljana and the University Medical Center Ljubljana, performed an autopsy on a fetus with microcephaly. A woman from Slovenia who had been employed as an aid worker in Brazil for the past couple of years became pregnant in February 2015. A few months later, she contracted Zika and later decided to return to Slovenia. An ultrasound at 29 weeks of her pregnancy revealed possible brain anomalies in the fetus. Microcephaly was later confirmed and she chose to terminate the pregnancy. Analysis of the brain tissue showed profound brain abnormalities, said Tatjana Avšič Županc, senior author on the paper. The group also found high concentrations of viral particles in the brain tissue — but no evidence of Zika anywhere else. “We think that this really represents the most compelling evidence to date that congenital CNS [central nervous system] malformations are associated with Zika virus,” Avšič Županc said. Dr. Albert Ko, who has been working in Brazil investigating the rise in microcephaly cases, said the Slovenian findings are consistent with what is being seen in that country. Ko, a professor at Yale’s School of Public Health, said the condition of the fetal brain described in the Slovenian paper was very concerning. He suggested the type of damage seen would likely translate into a poor prognosis for a child. Ko and some colleagues reported Tuesday in the journal JAMA Ophthalmology that a number of Brazilian babies born with microcephaly suspected to be linked to Zika infection also have damage to their eyes. Ko said he fears there will be a spectrum of birth defects associated with this virus, some of which remain to be identified. As for the questions of whether Zika infection is causing microcephaly in some infants, Zaki said that while it is important to gather more evidence, finding Zika virus in the tissues of a growing number of malformed brains is very persuasive. “To me as a pathologist, this is undoubtedly evidence that it’s causing it,” he said. Helen Branswell can be reached at [email protected] Follow Helen on Twitter @HelenBranswell

Exclusive: Miscarriages reported in 3 American women with Zika virusTwitterFacebookLinkedInEmailPrintFELIPE DANA/AP Brain scans of a baby born with microcephaly at the Oswaldo Cruz Hospital in Recife, Brazil. By HELEN BRANSWELL @HelenBranswell FEBRUARY 10, 2016 http://www.statnews.com/2016/02/10/zika-american-women-miscarriages/

Zika confirmed in Lehigh University student A lab worker holds a vial containing mosqitoes of the species Aedes aegypti that are known to carry Zika virus, on Feb/ 10, 2016, at the International Atomic Energy Agency Laboratories in Seibersdorf, south of Vienna, Austria. Lehigh University said the same day one of its students who had traveled abroad over winter break contracted the virus. (Getty Images | For lehighvalleylive.com)PrintEmailBy Kurt Bresswein | For lehighvalleylive.com Email the author | Follow on Twitter on February 10, 2016 at 6:38 PM, updated February 10, 2016 at 7:12 PM2shares A Lehigh University student who traveled abroad over winter break has tested positive for Zika amid a continuing outbreak of the virus. The Bethlehem school announced the diagnosis in an email Wednesday evening to the Lehigh community, university spokeswoman Lori Friedman said. The Pennsylvania Department of Health relayed the positive test to Lehigh, Vice-Provost for Student Affairs John Smeaton said in the email. "We are grateful to be able to report that the student has recovered and is feeling well," Smeaton wrote. "The Lehigh University Health and Wellness Center has been in direct contact with state health officials, who indicate that there is no additional health risk to anyone on campus." Friedman would not comment on whether the student was one of two female Pennsylvania residents who, the state Department of Health said Tuesday, had contracted the state's first confirmed cases of Zika. Zika confirmed in two Pennsylvania residents Known to spread through mosquito bites, the virus linked to a birth defect is also spread from mother to child, in blood transfusions and through sexual contact. State health officials were not immediately available for comment Wednesday evening on Lehigh's announcement. The state announcement Tuesday on the diagnoses included no further details about the two cases, in an effort to protect patient privacy. This Zika outbreak began in May 2015 and is occurring in many countries. Generally a mild illness, Zika is known to spread primarily through the bite of an infected mosquito. But in rare cases it has been known to also spread from mother to child, as well as through blood transfusion. Sexual transmission of Zika virus is possible, and men who have traveled to affected areas are advised to take steps to prevent the spread of Zika virus through sexual contact. "No locally transmitted Zika cases have been reported in the continental United States, but cases have been reported in returning travelers," Lehigh says in a Zika update on its Student Affairs website. Ana Beatriz, a 4-month-old girl with microcephaly, a feared complication of the Zika virus, is seen Feb. 8, 2016, in Lagoa do Carro, Pernambuco, Brazil. (European Pressphoto Agency | For lehighvalleylive.com) Concern about the virus was elevated following reports of increased cases of a serious birth defect known as microcephaly that may be associated with Zika virus infection among pregnant women. Children born with the untreatable disorder suffer from disproportionately small skulls. Lehigh's email to its campus community included a link to a U.S. Centers for Disease Control and Prevention question-and-answer feature on the virus. The university advises contacting Lehigh's Health and Wellness Center if anyone exhibits symptoms of the disease – including fever, rash, conjunctivitis and joint pain – within two week of travel to an area of concern. Kurt Bresswein may be reached at [email protected]. Follow him on Twitter @KurtBresswein. Find lehighvalleylive.com on Facebook. http://www.lehighvalleylive.com/bethlehem/index.ssf/2016/02/zika_confirmed_in_lehigh_unive.html

LOCAL FEBRUARY 10, 2016 3:46 PM Yolo County confirms case of Zika virusRead more here: http://www.sacbee.com/news/local/article59651061.html#storylink=cpyBY SAMMY CAIOLA [email protected] A Yolo County person has tested positive for Zika virus after recently returning from international travel, according to a county news release issued Wednesday. The announcement didn’t mention the identity or sex of the infected person or where they traveled to. The World Health Organization has declared the Zika virus a global public health emergency. It’s spread to 20 countries in Central and South America and the Caribbean, including Mexico. Researchers suspect it causes a severe neurological condition called microcephaly in babies of infected mothers. The California Department of Public Health has reported six travel-associated cases of Zika in California since 2013, including two in 2015, as of Feb. 5. There have been 35 travel-associated cases in the U.S. since 2015, and no reports of local transmission. Zika can be transmitted by the aedes mosquito, which is common in tropical climates but exists in low concentrations in Northern California. There have been some reports of Zika transmission through blood or sexual fluids. “Yolo County residents traveling to Central or South America or the Caribbean, where Zika is present, should take precautions against mosquitoes,” said Yolo County Health Officer Dr. Ron Chapman in the news release. “If you are pregnant, consider postponing your trip.” http://www.sacbee.com/news/local/article59651061.html Read more here: http://www.sacbee.com/news/local/article59651061.html#storylink=cpy

COUNTY PRESS RELEASESPrintFeedbackShare & BookmarkRSSConfirmed Zika Case in Yolo CountyPost Date:02/10/2016 3:20 PMPress Release (Woodland, CA) – The Centers for Disease Control and Prevention (CDC) confirmed today that a Yolo County resident has tested positive for Zika virus. This individual recently traveled out of the country and had a mild case of Zika. Zika virus is a relatively new disease for the Western hemisphere. It first appeared in Brazil in May of 2015. It has since spread to 20 countries in Central and South America and the Caribbean, including Mexico. Zika is spread through mosquito bites, not casual person-to-person contact. According to the CDC, the most common symptoms are fever, rash, joint pain and red, itchy eyes. Symptoms are usually mild and last several days to a week. Many people who have Zika will not experience symptoms. There is currently no vaccine or treatment for Zika. Pregnant women, however, are believed to be most at risk for complications from the Zika virus because serious birth defects have been reported in infants born to women infected with the virus. The CDC is planning studies to learn more about the connection between Zika and children born with these birth defects. In the meantime, the CDC has issued travel guidance for women who are pregnant or who may become pregnant. To stay up-to-date on the CDC’s latest travel notices, visit:www.cdc.gov/travel. “Yolo County residents traveling to Central or South America or the Caribbean, where Zika is present, should take precautions against mosquitoes,” said Yolo County Health Officer Ron Chapman, MD, MPH. “If you are pregnant, consider postponing your trip. All travelers to areas where Zika is present should go to their doctor if they experience any of the symptoms associated with Zika within three to seven days after they return. Pregnant women who have recently traveled to an area with Zika should talk to a healthcare provider about their travel even if they don’t feel sick.” Ways to avoid mosquito bites include: • Using an insect repellant containing DEET, picaridin, IR3535 or oil of lemon eucalyptus; • Wearing long-sleeved shirts and trousers; • Using air conditioning or window and door screens to keep mosquitoes outside; and • Reducing the number of mosquitoes inside and outside your home by emptying standing water from containers such as flowerpots or buckets. Mosquitoes can breed in as little amount of water as a bottle cap. To learn more about Zika virus, visit: www.cdc.gov/zika and www.cdph.ca.gov/HealthInfo/discond/Pages/Zika.aspx. http://www.yolocounty.org/Home/Components/News/News/3330/26?backlist=%2fhealth-human-services

Map update https://www.google.com/maps/d/edit?hl=en&hl=en&authuser=0&authuser=0&mid=zv94AJqgUct4.kT4qLMXp3SLU

ByVannessa MaravillaYolo County resident tests positive for Zika virusOfficials said resident recently traveled out of U.SUPDATED 3:50 PM PST Feb 10, 2016NEXT STORY Police: Parents of student who brought gun to school arrested Text Size:AAAThe Centers for Disease Control and Prevention updated its Zika virus guidance for pregnant women on Feb. 3, advising them to protect themselves if their male sexual partner has traveled to or lives in an area where Zika virus is circulating. The update in recommendations comes one day after Dallas County, Texas, health officials, announced a case of the virus involving a patient who had sex with someone who had recently returned from Venezuela infected with the mosquito-borne virus. The CDC confirmed this as first known case of the virus being locally acquired in the continental United States in the current outbreak. CNNWOODLAND, Calif. (KCRA) —A Yolo county resident has tested positive for Zika virus, the Centers for Disease Control and Prevention said. RELATED Car crash in closes 2 lanes at... Female tiger killed by mating partner... The Riggs Report: New Hampshire's... Sac police arrest man accused in 2... Strange smell forces evacuations at...The resident had recently traveled out of the country and contracted a mild case of Zika. Zika virus is spread through mosquito bites. The virus has spread to 20 countries in Central and South America, Mexico and the Caribbean. According to the CDC, the most common symptoms of ZIka are fever, rash, joint pain and red, itchy eyes. These symptoms are usually mild, but can last several days to a week. Many people who have Zika will not experience symptoms. There is currently no vaccine or treatment for Zika. Officials said pregnant women are believed to be the most at risk for complications from the Zika virus because serious birth defects have been reported in infants born to women infected with the virus. “Yolo County residents traveling to Central or South America or the Caribbean, where Zika is present, should take precautions against mosquitoes,” Yolo County Health Officer Dr. Ron Chapman said. “If you are pregnant, consider postponing your trip. All travelers to areas where Zika is present should go to their doctor if they experience any of the symptoms associated with Zika within three to seven days after they return. Pregnant women who have recently traveled to an area with Zika should talk to a health care provider about their travel even if they don’t feel sick.” Stay with KCRA News for the latest on this developing story

http://www.kcra.com/news/local-news/news-sacramento/yolo-county-resident-tests-positive-for-zika-virus/37929486 ]

REFERENCES 1 Dick GW, Kitchen SF, Haddow AJ. Zika virus. I. Isolations and serological specificity.Trans R Soc Trop Med Hyg 1952;46:509-520 CrossRef | Web of Science | Medline 2 Hayes EB. Zika virus outside Africa. Emerg Infect Dis 2009;15:1347-1350 CrossRef | Web of Science | Medline 3 Duffy MR, Chen TH, Hancock WT, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med 2009;360:2536-2543 Free Full Text | Web of Science | Medline 4 Cao-Lormeau VM, Roche C, Teissier A, et al. Zika virus, French Polynesia, South Pacific, 2013. Emerg Infect Dis 2014;20:1085-1086 Web of Science | Medline 5 Rapid risk assessment: Zika virus epidemic in the Americas: potential association with microcephaly and Guillain-Barré syndrome. Stockholm: European Centre for Disease Prevention and Control, December 10, 2015 (http://ecdc.europa.eu/en/publications/Publications/zika-virus-americas-association-with-microcephaly-rapid-risk-assessment.pdf). 6 Ioos S, Mallet HP, Leparc Goffart I, Gauthier V, Cardoso T, Herida M. Current Zika virus epidemiology and recent epidemics. Med Mal Infect 2014;44:302-307 CrossRef | Web of Science | Medline 7 Faye O, Faye O, Diallo D, Diallo M, Weidmann M, Sall AA. Quantitative real-time PCR detection of Zika virus and evaluation with field-caught mosquitoes. Virol J 2013;10:311-311 CrossRef | Web of Science | Medline 8 Faye O, Faye O, Dupressoir A, Weidmann M, Ndiaye M, Alpha Sall A. One-step RT-PCR for detection of Zika virus. J Clin Virol 2008;43:96-101 CrossRef | Web of Science | Medline 9 Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol 2013;30:2725-2729 CrossRef | Web of Science | Medline 10 Oliveira Melo AS, Malinger G, Ximenes R, Szejnfeld PO, Alves Sampaio S, Bispo de Filippis AM. Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg? Ultrasound Obstet Gynecol 2016;47:6-7 CrossRef | Web of Science | Medline 11 Macdonald EM, Koval JJ, Natale R, Regnault T, Campbell MK. Population-based placental weight ratio distributions. Int J Pediatr 2014;2014:291846-291846 CrossRef 12 Alpert SG, Fergerson J, Noël LP. Intrauterine West Nile virus: ocular and systemic findings. Am J Ophthalmol 2003;136:733-735 CrossRef | Web of Science | Medline 13 Tsai TF. Congenital arboviral infections: something new, something old. Pediatrics2006;117:936-939 CrossRef | Web of Science | Medline 14 Chi JG, Dooling EC, Gilles FH. Gyral development of the human brain. Ann Neurol1977;1:86-93 CrossRef | Web of Science | Medline 15 Goldsmith CS, Ksiazek TG, Rollin PE, et al. Cell culture and electron microscopy for identifying viruses in diseases of unknown cause. Emerg Infect Dis 2013;19:886-891 CrossRef | Web of Science | Medline 16 Gillespie LK, Hoenen A, Morgan G, Mackenzie JM. The endoplasmic reticulum provides the membrane platform for biogenesis of the flavivirus replication complex. J Virol2010;84:10438-10447 CrossRef | Web of Science | Medline 17 Lanciotti RS, Kosoy OL, Laven JJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis 2008;14:1232-1239 CrossRef | Web of Science | Medline 18 Musso D, Roche C, Robin E, Nhan T, Teissier A, Cao-Lormeau VM. Potential sexual transmission of Zika virus. Emerg Infect Dis 2015;21:359-361 CrossRef | Web of Science | Medline 19 Faye O, Freire CC, Iamarino A, et al. Molecular evolution of Zika virus during its emergence in the 20th century. PLoS Negl Trop Dis 2014;8:e2636-e2636 CrossRef | Medline

DISCUSSIONThis case shows severe fetal brain injury associated with ZIKV infection with vertical transmission. Recently, ZIKV was found in amniotic fluid of two fetuses that were found to have microcephaly, which was consistent with intrauterine transmission of the virus.10Described cases are similar to the case presented here and were characterized by severely affected CNS and gross intrauterine growth retardation. Calcifications in the placenta and a low placental–fetal weight ratio,11 which were seen in this case, indicate potential damage to the placenta by the virus. Among the few reports of teratogenic effects of flaviviruses, investigators described the brain and eyes as the main targets.12,13 No presence of virus and no pathological changes were detected in any other fetal organs apart from the brain, which suggests a strong neurotropism of the virus. The localization of immunofluorescence signal and the morphologic appearance of the calcifications, which resembled destroyed neuronal structures, indicate a possible location of the virus in neurons. The consequent damage might cause arrested development of the cerebral cortex at the embryonic age of approximately 20 weeks.14 The mechanism involved in the neurotropism of ZIKV is currently not clear. The association between ZIKV infection and fetal brain anomalies was also noted by findings on electron microscopy that were consistent with ZIKV detection in the fetal brain. Dense particles consistent with ZIKV were seen in damaged endoplasmic reticulum. Groups of enveloped structures with a bright interior resembling the remains of replication complexes that are characteristic of flaviviruses15,16 indicate viral replication in the brain. The findings on electron microscopy suggest a possible persistence of ZIKV in the fetal brain, possibly because of the immunologically secure milieu for the virus. The number of viral copies that were detected in the fetal brain were substantially higher than those reported in the serum obtained from adult ZIKV-infected patients17 but similar to those reported in semen samples.18 The complete genome sequence of ZIKV that was recovered in this study is consistent with the observation that the present strain in Brazil has emerged from the Asian lineage.19 The presence of two major amino acid substitutions positioned in nonstructural proteins NS1 and NS4B probably represents an accidental event or indicates a process of eventual adaptation of the virus to a new environment. Further research is needed to better understand the potential implications of these observations. It is likely that the rapid spread of ZIKV around the globe will be a strong impetus for collaborative research on the biologic properties of the virus, particularly since the risk of neurotropic and teratogenic virus infections places a high emotional and economic burden on society. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. This article was published on February 10, 2016, at NEJM.org. We thank the patient in this case for her willingness to provide detailed medical and immunologic data; Miha Juvan for processing of brain photographs; Peter Štrafela for his assistance with the neuropathological analyses; Martin Sagadin, Tina Uršič, Nataša Toplak, Simon Koren, and Andrej Steyer for their assistance in virus detection, sequencing, and analysis of next-generation sequencing data; Mateja Jelovšek for her assistance in comprehensive serologic investigations, and Luca Lovrečič and Marija Volk for their assistance in molecular karyotyping with microarray testing.

RESULTSAutopsy and Neuropathological FindingsThe fetal body weight was 1470 g (5th percentile), the length 42 cm (10th percentile), and the head circumference 26 cm (1st percentile). The only external anomaly that was noted was microcephaly. The placenta weighed 200 g, resulting in a placental–fetal weight ratio of 0.136 (<3rd percentile). Macroscopic examination of the CNS revealed micrencephaly with a whole-brain weight of 84 g (4 SD below average), widely open sylvian fissures, and a small cerebellum and brain stem. Almost complete agyria and internal hydrocephalus of the lateral ventricles were observed. There were numerous variable-sized calcifications in the cortex and subcortical white matter in the frontal, parietal, and occipital lobes. The subcortical nuclei were quite well developed (Figure 1C and 1D). In spite of some autolysis, microscopic examination revealed appropriate cytoarchitecture of the fetal brain. The most prominent histopathological features were multifocal collections of filamentous, granular, and neuron-shaped calcifications in the cortex and subcortical white matter with focal involvement of the whole cortical ribbon, occasionally associated with cortical displacement (Figure 2A and 2BFIGURE 2Microscopic Analysis of Brain Tissue.). Diffuse astrogliosis was present with focal astrocytic outburst into the subarachnoid space, mostly on the convexity of the cerebral hemispheres (Figure 2C). Activated microglial cells and some macrophages expressing HLA-DR were present throughout most of the cerebral gray and white matter (Figure 2D). Scattered mild perivascular infiltrates composed of T cells and some B cells were present in the subcortical white matter (Fig. S1 in the Supplementary Appendix). The cerebellum, brain stem, and spinal cord showed neither inflammation nor dystrophic calcifications. The brain stem and spinal cord showed Wallerian degeneration of the long descending tracts, especially the lateral corticospinal tract, whereas ascending dorsal columns were well preserved (Figure 2E). Indirect immunofluorescence revealed granular intracytoplasmic reaction in destroyed neuronal structures, which pointed to a possible location of the virus in neurons (Figure 2F, and Fig. S1 in the Supplementary Appendix). Histologic examination of the placenta confirmed focal calcifications in villi and decidua, but no inflammation was found. There were no relevant pathological changes in other fetal organs or in the umbilical cord or fetal membranes. Fetal karyotyping with the use of microarray technology showed a normal 46XY (male) profile. Electron MicroscopyAlthough analysis of the ultrathin sections of the brain showed poorly preserved brain tissue with ruptured and lysed cells, clusters of dense virus-like particles of approximately 50 nm in size were found in damaged cytoplasmic vesicles. Groups of enveloped structures with a bright interior were also detected. At the periphery of such groups, the remains of membranes could be seen. Negative staining of homogenized brain revealed spherical virus particles measuring 42 to 54 nm with morphologic characteristics consistent with viruses of the Flaviviridae family (Figure 3FIGURE 3Electron Microscopy of Ultrathin Sections of Fetal Brain and Staining of a Flavivirus-like Particle.). Microbiologic InvestigationPositive results for ZIKV were obtained on RT-PCR assay only in the fetal brain sample, where 6.5×107 viral RNA copies per milligram of tissue were detected. In addition, all autopsy samples were tested on PCR assay and were found to be negative for other flaviviruses (dengue virus, yellow fever virus, West Nile virus, and tick-borne encephalitis virus), along with chikungunya virus, lymphocytic choriomeningitis, cytomegalovirus, rubella virus, varicella–zoster virus, herpes simplex virus, parvovirus B19, enteroviruses, and Toxoplasma gondii (Table S2 in the Supplementary Appendix). A complete ZIKV genome sequence (10,808 nucelotides) was recovered from brain tissue. Phylogenetic analysis showed the highest identity (99.7%) with the ZIKV strain isolated from a patient from French Polynesia in 2013 (KJ776791) and ZIKV detected in Sao Paolo, Brazil, in 2015 (KU321639), followed by a strain isolated in Cambodia in 2010 (JN860885, with 98.3% identity) and with a strain from the outbreak in Micronesia in 2007 (EU545988, with 98% identity) (Figure 4FIGURE 4Phylogenetic Analysis of the Complete Genome of Zika Virus.). In the ZIKV polyprotein, 23 polymorphisms were detected in comparison with the strain from Micronesia and 5 polymorphisms in comparison with the isolate from French Polynesia; three amino acid changes were found in the NS1 region (K940E, T1027A, and M1143V), one in the NS4B region (T2509I), and one in the FtsJ-like methyltransferase region (M2634V).

METHODSAutopsy and Central Nervous System (CNS) ExaminationAn autopsy of the fetus and placenta was performed 3 days after termination of the pregnancy, with an extensive sampling of all organs, placenta, and umbilical cord. Samples were fixed in 10% buffered formalin and embedded in paraffin. Fresh tissue samples were collected for microbiologic investigations. Brain and spinal cord were fixed in 27% buffered formalin for 3 weeks, after which a neuropathological examination was performed with extensive sampling of the brain and spinal cord. Sections of all tissue samples were stained with hematoxylin and eosin. Immunostaining for glial fibrillary acid protein, neurofilament, human leukocyte antigen DR (HLA-DR), CD3 (to highlight T cells), and CD20 (to highlight B cells) was performed on representative CNS samples. Electron MicroscopyTissue was collected from formalin-fixed brain and underwent fixation in 1% osmium tetroxide and dehydration in increasing concentrations of ethanol. The sample was then embedded in Epon. Semithin sections (1.4 μm) were made, stained with Azur II, and analyzed by means of light microscopy. Ultrathin sections (60 nm) were stained with uranyl acetate and lead citrate. In addition, a small piece of brain (5 mm3) was homogenized in buffer. The suspension was then cleared by low-speed centrifugation, and the obtained supernatant was ultracentrifuged directly onto an electron microscopic grid with the use of an Airfuge (Beckman Coulter). Negative staining was performed with 1% phosphotungstic acid. Imaging of the ultrathin sections and brain homogenate was performed with the use of a 120-kV JEM-1400Plus transmission electron microscope (JEOL). Indirect ImmunofluorescenceParaffin-embedded sections of the fetal brain tissue and brain tissue of an autopsied man as a negative control were incubated with serum obtained from the mother of the fetus (dilution, 1:10), followed by antihuman IgG antibodies labeled with fluorescein isothiocyanate (FITC) (dilution, 1:50). In addition, fetal brain tissue was incubated with a serum obtained from a healthy blood donor, as well as with FITC-labeled antihuman IgG antibodies only. Microbiologic InvestigationRNA was extracted from 10 mg of the placenta, lungs, heart, skin, spleen, thymus, liver, kidneys, and cerebral cortex with the use of a TRIzol Plus RNA purification kit (Thermo Fisher Scientific). Real-time RT-PCR for the detection of ZIKV RNA (NS5) and one-step RT-PCR for the detection of the envelope-protein coding region (360 bp) were performed as described previously.7,8 In addition, next-generation sequencing was performed in samples of fetal brain tissue with the use of Ion Torrent (Thermo Fisher Scientific) and Geneious software, version 9.0.6. Reads from both runs were combined and mapped to the reference sequence (ZIKV MR766; LC002520) with the use of default measures. For phylogenetic analysis, complete-genome ZIKV sequences were used, and multiple sequence alignments (ClustalW) were performed. A neighbor-joining phylogenetic tree (GTR+G+I model) was constructed, with the use of the MEGA6 software system,9 to show the phylogenetic relationships. The nucleotide sequence of ZIKV that was obtained in this study has been deposited in GenBank under accession number KU527068. A detailed description of the molecular methods is provided in the Supplementary Appendix, available with the full text of this article at NEJM.org. The results of comprehensive serologic analyses of maternal serum and a description of the molecular differential diagnostic procedures used with fetal tissue samples are provided in Tables S1 and S2 in the Supplementary Appendix. All the authors vouch for the completeness and accuracy of the data and analyses presented.

CASE REPORTIn mid-October 2015, a 25-year-old previously healthy European woman came to the Department of Perinatology at the University Medical Center in Ljubljana, Slovenia, because of assumed fetal anomalies. Since December 2013, she had lived and worked as a volunteer in Natal, the capital of Rio Grande do Norte state. She had become pregnant at the end of February 2015. During the 13th week of gestation, she had become ill with high fever, which was followed by severe musculoskeletal and retroocular pain and an itching, generalized maculopapular rash. Since there was a ZIKV epidemic in the community, infection with the virus was suspected, but no virologic diagnostic testing was performed. Ultrasonography that was performed at 14 and 20 weeks of gestation showed normal fetal growth and anatomy. The patient returned to Europe at 28 weeks of gestation. Ultrasonographic examination that was performed at 29 weeks of gestation showed the first signs of fetal anomalies, and she was referred to the Department of Perinatology. At that time, she also noticed reduced fetal movements. Ultrasonography that was performed at 32 weeks of gestation confirmed intrauterine growth retardation (estimated third percentile of fetal weight) with normal amniotic fluid, a placenta measuring 3.5 cm in thickness (normal size) with numerous calcifications, a head circumference below the second percentile for gestation (microcephaly), moderate ventriculomegaly, and a transcerebellar diameter below the second percentile. Brain structures were blurred, and there were numerous calcifications in various parts of the brain (Figure 1A and 1BFIGURE 1Prenatal Ultrasonographic Images and Photographs of Coronal Slices of Brain.). There were no other obvious fetal structural abnormalities. Fetal, umbilical, and uterine blood flows were normal on Doppler ultrasonography. The clinical presentation raised suspicion of fetal viral infection. Because of severe brain disease and microcephaly, the fetus was given a poor prognosis for neonatal health. The mother requested that the pregnancy be terminated, and the procedure was subsequently approved by national and hospital ethics committees. Medical termination of the pregnancy was performed at 32 weeks of gestation. At the delivery, the only morphologic anomaly was the prominent microcephaly. Genetic consultation that included a detailed maternal family history revealed no suspicion of genetic syndromes or diseases. An autopsy was performed, as is mandatory in all cases of termination of pregnancy. The mother provided written informed consent for the publication of this case report.

ZIKV, an emerging mosquito-borne flavivirus, was initially isolated from a rhesus monkey in the Zika forest in Uganda in 1947.1 It is transmitted by various species of aedes mosquitoes. After the first human ZIKV infection, sporadic cases were reported in Southeast Asia and sub-Saharan Africa.2 ZIKV was responsible for the outbreak in Yap Island of Micronesia in 2007 and for major epidemics in French Polynesia, New Caledonia, the Cook Islands, and Easter Island in 2013 and 2014.3,4 In 2015, there was a dramatic increase in reports of ZIKV infection in the Americas. Brazil is the most affected country, with preliminary estimates of 440,000 to 1.3 million cases of autochthonous ZIKV infection reported through December 2015.5 The classic clinical picture of ZIKV infection resembles that of dengue fever and chikungunya and is manifested by fever, headache, arthralgia, myalgia, and maculopapular rash, a complex of symptoms that hampers differential diagnosis. Although the disease is self-limiting, cases of neurologic manifestations and the Guillain–Barré syndrome were described in French Polynesia and in Brazil during ZIKV epidemics.5,6 Recent reports from the Ministry of Health of Brazil suggest that cases of microcephaly have increased by a factor of approximately 20 among newborns in the northeast region of the country, which indicates a possible association between ZIKV infection in pregnancy and fetal malformations.5 We present a case of vertical transmission of ZIKV in a woman who was probably infected with ZIKV in northeastern Brazil at the end of the first trimester of pregnancy. Our discussion includes details of fetal imaging and pathological and virologic analyses.

A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain.

Jernej Mlakar, M.D., Misa Korva, Ph.D., Nataša Tul, M.D., Ph.D., Mara Popović, M.D., Ph.D., Mateja Poljšak-Prijatelj, Ph.D., Jerica Mraz, M.Sc., Marko Kolenc, M.Sc., Katarina Resman Rus, M.Sc., Tina Vesnaver Vipotnik, M.D., Vesna Fabjan Vodušek, M.D., Alenka Vizjak, Ph.D., Jože Pižem, M.D., Ph.D., Miroslav Petrovec, M.D., Ph.D., and Tatjana Avšič Županc, Ph.D. February 10, 2016DOI: 10.1056/NEJMoa1600651 SOURCE INFORMATIONFrom the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana — all in Ljubljana, Slovenia. Address reprint requests to Dr. Avšič Županc at the Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Zaloška 4, Ljubljana 1000, Slovenia, or at [email protected].

Zika Virus Associated with Microcephaly - NEJM http://www.nejm.org/doi/full/10.1056/NEJMoa1600651?query=featured_home#t=articleTop

ZIKA VIRUS CASE CONFIRMED AT LEHIGH UNIVERSITYUpdated 1 hr 8 mins ago http://6abc.com/health/zika-virus-case-confirmed-at-lehigh-university/1195315/ BETHLEHEM, Pa. (WPVI) --Lehigh University has confirmed one of their students has tested positive for the Zika virus. The school says the student had traveled abroad over the winter break. "The Lehigh University Health and Wellness Center has been in direct contact with state health officials, who indicate that there is no additional health risk to anyone on campus," a statement released on the school's website says. This comes one day after Pennsylvania health officials said two state residentswere diagnosed with the Zika virus. It's not known if the Lehigh University student is one of those two people. The University also posted the notice on their Facebook page.

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MESSAGE FROM THE DIRECTORWelcome to the Lehigh University Health and Wellness Center, which provides acute and ongoing care to approximately 4,800 undergraduate students and over 2,000 graduate students. Our dedicated, professional staff offers a host of services, including acute care, routine examinations, immunizations, lab services, gynecological examinations and contraceptive counseling. We also have a wellness resource area with over-the-counter medications, and a relaxation room with massage chairs. No appointment is necessary for these services Our goals are to help individuals stay healthy in pursuit of academic success, and to foster the public health of the campus community. SUSAN C. KITEI, MDDirector, Student Health Services ZIKA VIRUS UPDATE 2.10.16, 4:45 PM: Message to Lehigh Community Regarding Zika Virus Dear Students, Staff and Faculty, We have been informed by the Pennsylvania Department of Health that one of our students who traveled abroad over the winter break has tested positive for the Zika virus. We are grateful to be able to report that the student has recovered and is feeling well. The Lehigh University Health and Wellness Center has been in direct contact with state health officials, who indicate that there is no additional health risk to anyone on campus. A Q & A developed by the Centers for Disease Control and Prevention can provide more background on the Zika virus: http://www.cdc.gov/zika/disease-qa.html. Sincerely, John Smeaton Vice-Provost of Student Affairs ZIKA VIRUS UPDATE 2.10.16:Lehigh continues to monitor the Zika virus outbreak in various countries. No locally transmitted Zika cases have been reported in the continental United States, but cases have been reported in returning travelers. Lehigh would like to advise members of the Lehigh community who are considering traveling in areas with the Zika virus to be aware and to take precautions. Updated information about Zika outbreaks around the globe can be found athttp://wwwnc.cdc.gov/travel/page/zika-travel-information. If you are traveling to areas with active Zika virus transmission, the Centers for Disease Control and Prevention (CDC) advise preventive measures to avoid mosquito bites such as wearing long sleeves and long pants, staying in screened or air-conditioned places, applying government-registered bug repellents and using mosquito nets when sleeping. You can read more about these suggestions on the CDC website at http://www.cdc.gov/zika/prevention/. Any individuals who are pregnant or trying to become pregnant should consider avoiding or postponing travel to the affected areas. More information can also be found at: Centers for Disease Control and Prevention: http://www.cdc.gov/zika World Health Organization: http://www.who.int/topics/zika/en/ U.S. State Department: https://www.travel.state.gov/content/passports/en/go/Zika.html We will continue to monitor this situation. Anyone exhibiting symptoms of the disease – which includes fever, rash, conjunctivitis and joint pain – within two week of travel to an area of concern should contact the Lehigh University Health and Wellness Center for an appointment. Be sure to tell your health care provider when and where you have traveled. http://studentaffairs.lehigh.edu/health

Zika virus: 'Strongest evidence yet' of effect on babies22 minutes ago From the sectionLatin America & CaribbeanImage copyrightAFPImage captionAuthorities in some countries affected by the virus have advised women to delay pregnancyZika virusZika outbreak: What you need to knowZika outbreak: Travel adviceZika outbreak: The perfect mosquitoVideo How mums-to-be are tackling ZikaOne of the US's most senior public health officials has revealed the "strongest evidence to date" of the effect on babies of the Zika virus. Dr Tom Frieden, head of the Center for Disease Control (CDC), was testifying before politicians in Washington. He said that data from the cases of two infants in Brazil who died soon after birth indicated the virus had passed from mother to child. However, he said the suspected link was still not definite. There are thought to have been more than 4,000 cases in Brazil alone of babies born with microcephaly - abnormally small brains - and where the transmission of Zika virus from mother to child is suspected of being the cause. Dr Frieden said intensive research was under way to find out much more about the mosquito-borne virus and to develop a vaccine for it, although he warned that that could still be years away. "We will likely see significant numbers of [Zika] cases in Puerto Rico and other US territories," Dr Frieden warned. He said the CDC would issue grants to US states at risk of Zika to better control mosquitoes. Also on Wednesday, the World Health Organization (WHO), which has called the outbreak a "global public health emergency", issued guidance for women on how to protect themselves. It said that until more is known on whether sexual contact can transmit Zika, "all men and women living in or returning from an area where Zika is present - especially pregnant women and their partners - should be counselled on the potential risks of sexual transmission and ensure safe sexual practices". "These include the correct and consistent use of condoms, one of the most effective methods of protection against all sexually transmitted infections," the WHO said. The use of contraception is a controversial issue in the region because of the Catholic Church's stance against it. However, the Church has rejected calls from liberal Catholics for a softening of its position on the issue in light of the outbreak. "Microcephaly has been occurring in Brazil for years. They are taking advantage of this moment to reintroduce the abortion topic," Bishop Leonardo Ulrich Steiner, secretary general of the Brazilian Bishops' Conference, told the Estado de Sao Paulo newspaper. The WHO said it was not advocating travel restrictions to the area but advised pregnant women, or those trying to become pregnant, to seek medical advice before travelling to areas where Zika is present. http://www.bbc.com/news/world-latin-america-35543371

February 10, 2016 | View Online The February 2016 Zika Virus Special Edition of DCHHS' Newsletter, Public Health Preparedness Update, is now available online."This newsletter is designed to inform the community about the latest news and information about public health activities in Dallas County," DCHHS Director Zachary Thompson said. Stories in the February 2016 Zika Virus Special Edition edition include:· DCHHS Reports First Three Cases of Zika Virus · DCHHS Starts Zika Campaign, CHIKV and Dengue Included · Countries and Territories with Active Zika Virus Transmission · Help Protect Yourself and Dallas County from Mosquito Viruses from Other Areas · Zika Virus Information Available in 10 Languages · Federal Agency Publishes DCHHS Fact Sheets · Zika Task Force Created for Seamless Response · DCHHS Lab on Target to Provide Zika Testing

Global scientific community commits to sharing data on Zika10 February 2016 Leading global health bodies including academic journals, NGOs, research funders and institutes, have committed to sharing data and results relevant to the current Zika crisis and future public health emergencies as rapidly and openly as possible.Organisations including the Bill and Melinda Gates Foundation, Médecins Sans Frontières, the US National Institute of Health and the Wellcome Trust, along with leading academic journals including Nature, Science and the New England Journal of Medicine, have signed a joint declaration and hope that other bodies will come on board in the coming weeks. The statement is intended to ensure that any information that might have value in combatting the Zika outbreak is made available to the international community, free of charge, as soon as is feasibly possible. Journal signatories provide assurance that doing so will not preclude researchers from subsequently publishing papers in their titles. It follows a consensus statement arising from a WHO consultation in September 2015, in which leading international stakeholders from multiple sectors affirmed that timely and transparent pre-publication sharing of data and results during public health emergencies must become the global norm. Dr Jeremy Farrar, Director of the Wellcome Trust and a signatory of the statement, said: “Research is an essential part of the response to any global health emergency. This is particularly true for Zika, where so much is still unknown about the virus, how it is spread and the possible link with microcephaly. “It’s critical that as results become available they are shared rapidly in a way that is equitable, ethical and transparent. This will ensure that the knowledge gained is turned quickly into health interventions that can have an impact on the epidemic. “It’s extremely heartening to see so many leading international organisations united in this unprecedented commitment to open science, reinforcing the decision by the WHO to declare Zika a Public Health Emergency of International Concern.” Statement on Data Sharing in Public Health Emergencies: The arguments for sharing data, and the consequences of not doing so, have been thrown into stark relief by the Ebola and Zika outbreaks. In the context of a public health emergency of international concern, there is an imperative on all parties to make any information available that might have value in combatting the crisis. We are committed to working in partnership to ensure that the global response to public health emergencies is informed by the best available research evidence and data, as such: Journal signatories will make all content concerning the Zika virus free to access. Any data or preprint deposited for unrestricted dissemination ahead of submission of any paper will not pre-empt its publication in these journals.Funder signatories will require researchers undertaking work relevant to public health emergencies to set in place mechanisms to share quality-assured interim and final data as rapidly and widely as possible, including with public health and research communities and the World Health Organisation.We urge other organisations to make the same commitments. This commitment is in line with the consensus statement agreed at a WHO expert consultation on data sharing last year whereby researchers are expected to share data at the earliest opportunity, once they are adequately controlled for release and subject to any safeguards required to protect research participants and patients. Signatories to the Statement Academy of Medical Sciences, UK Bill and Melinda Gates Foundation Biotechnology and Biological Sciences Research Council (BBSRC) The British Medical Journal (BMJ) Bulletin of the World Health Organization Canadian Institutes of Health Research The Centers for Disease Control and Prevention Chinese Academy of Sciences Chinese Centre for Disease Control and Prevention The Department of Biotechnology, Government of India The Department for International Development (DFID) Deutsche Forschungsgemeinschaft (DFG) eLife The Economic and Social Research Council (ESRC) F1000 Fondation Mérieux Fundação Oswaldo Cruz (Fiocruz) The Institut Pasteur Japan Agency for Medical Research and Development (AMED) The JAMA Network The Lancet Médecins Sans Frontières/Doctors Without Borders (MSF) National Academy of Medicine National Institutes of Health, USA National Science Foundation, USA The New England Journal of Medicine (NEJM) PLOS Science Journals South African Medical Research Council Springer Nature UK Medical Research Council Wellcome Trust ZonMw - The Netherlands Organisation for Health Research and Development Credit: LSHTM, Wellcome Images Notes to Editors For further information contact: Hannah Isom Senior Media Officer Wellcome Trust T: (+44) 207 611 8898 M: (+44) 7860 948 890 E: [email protected] The Wellcome Trust is a global charitable foundation dedicated to improving health. We support bright minds in science, the humanities and the social sciences, as well as education, public engagement and the application of research to medicine. Our investment portfolio gives us the independence to support such transformative work as the sequencing and understanding of the human genome, research that established front-line drugs for malaria, and Wellcome Collection, our free venue for the incurably curious that explores medicine, life and art. www.wellcome.ac.uk http://www.wellcome.ac.uk/News/Media-office/Press-releases/2016/WTP060169.htm