niman

IntroductionOver the last 6 months, thousands of microcephalic babies have been delivered in Brazil, the country that is experiencing the highest Zika virus infection rates worldwide. Given the apparent pronounced effects of this vector-borne viral pathogen on the developing fetus, there is a rush to ascertain whether and how Zika virus might be causing microcephaly, as well as the need to address concerns regarding potential biases in the reporting of cases, or historic under-reporting of cases in Brazil and in other Zika virus-affected countries. Knowledge of mechanism could lead us to early detection methods and therapeutic responses to this new apparent teratogen and enhance preparedness for the next viral epidemic. We make a case for epidemiologists, virologists, pathologists, obstetricians, toxicologists, and developmental biologists to rigorously consider and test the role of the placenta as a mediator of the viral exposure and the cause of the fetal brain defects associated with Zika virus infection.

SummaryThe mechanism by which the Zika virus can cause fetal microcephaly is not known. Reports indicate that Zika is able to evade the normal immunoprotective responses of the placenta. Microcephaly has genetic causes, some associated with maternal exposures including radiation, tobacco smoke, alcohol, and viruses. Two hypotheses regarding the role of the placenta are possible: one is that the placenta directly conveys the Zika virus to the early embryo or fetus. Alternatively, the placenta itself might be mounting a response to the exposure; this response might be contributing to or causing the brain defect. This distinction is crucial to the diagnosis of fetuses at risk and the design of therapeutic strategies to prevent Zika-induced teratogenesis.

Jennifer J Adibi, ScD, Ernesto T A Marques Jr, MD, Abigail Cartus, BS, Richard H Beigi, MDPublished Online: 04 March 2016 DOI: http://dx.doi.org/10.1016/S0140-6736(16)00650-4 | Article InfoPublication HistoryPublished Online:04 March 2016

Teratogenic effects of the Zika virus and the role of the placentahttp://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00650-4/fulltext

ATCC Supporting Zika Virus Research Discover more at www.atcc.orgMANASSAS, Va., Feb. 5, 2016 /PRNewswire-USNewswire/ -- ATCC, the premier global biological materials resource and standards organization, is poised to assist the medical and life science researchers that are working to address the evolving concerns around Zika Virus infection. Zika virus is a single-stranded RNA virus of the Flaviviridae family, genus Flavivirus, which also includes the West Nile, Dengue and Chikungunya Viruses. Zika virus is transmitted to humans primarily through the bite of an infected Aedes species mosquito. For more information on the disease, please refer to the CDC website. The virus was first deposited into ATCC by Dr. Jordi Casals of the Rockefeller Foundation Virus Laboratory in 1953. Since that time ATCC has made the Zika virus (ATCC® VR-84™) strain MR766 available for research purposes to qualified scientists and laboratories, on a global basis, through a highly vetted process that requires them to demonstrate they have appropriate facilities and safety programs in place (in accordance with Biosafety in Microbiological and Biomedical Laboratories (BMBL) guidelines). ATCC is now working to respond to the greatly increased demand for the Zika virus in an effort to support a better understanding of its biology and to foster development of accurate and dependable diagnostic tests. In addition to ATCC, three stains of the Zika virus are available through BEI Resources, a NIAID Biorepository established to support basic research and develop improved diagnostic tests, vaccines, and therapies. Registration and approval is required by NIAID to obtain these viruses. www.beiresources.org As the biomedical and scientific communities continue to respond to the public health concerns represented by the Zika Virus, ATCC will work closely with them to ensure they have the research and biological reference materials they need for their work. For additional information, please refer to the Zika Virus FAQ on our website. About ATCC ATCC collaborates with and supports the scientific community with industry-standard products and innovative solutions. With the world's largest and most diverse collection of human and animal cell lines, molecular genomic tools, microorganisms, biological products, and standards ATCC is a trusted biological resource for the worldwide research community. Together, the people of ATCC share in its mission to acquire, authenticate, preserve, develop, and distribute biological materials and information for the advancement of scientific knowledge. Founded in 1925, ATCC is a non-profit organization with headquarters in Manassas, VA. Discover more at www.atcc.org. Logo - http://photos.prnewswire.com/prnh/20160112/321324LOGO SOURCE American Type Culture Collection RELATED LINKShttp://www.atcc.org http://www.prnewswire.com/news-releases/atcc-supporting-zika-virus-research-300216257.html

Lab tests reveal link between Zika and microcephalyUS scientists say they have discovered a evidence of a link between the Zika virus and brain deformation in fetuses. Tests revealed that the virus appeared to target cells crucial to brain development. Scientists claimed that laboratory tests had yielded the first evidence of a biological link between the virus and Zika. Studies showed the virus targeted cells that were important for the development of the brain, before disabling or destroying them. The findings provide a significant breakthrough in linking the mosquito-born pathogen with microcephaly, according to Guo-li Ming, a professor of neurology at Johns Hopkins' Institute for Cell Engineering, one of the report's co-authors. The research team used lab-grown human stem cells to look at which type of cells were selectively infected by the Zika virus. Scientists looked at three brain cell types, and found that 90 percent of human neural progenitor cells (hNPCs) were infected within three days - with many of them already dead within that time. Like other viruses, Zika hijacks cellular machinery to make copies of itself and eventually destroys infected host cells. 'Telling' pattern of infection The hNPCs are crucial for the development of the cortex - or outer layer - of fetal brains, and the findings would be consistent with the theory that Zika can cause microcephaly. Watch video12:07Brazil in battle against Zika virus"It is very telling that the cells that form the cortex are potentially susceptible to the virus," said Ming. Co-author Hongjun Song said that the results - published in the journal Stem Cell - would help identify new treatments. "Now that we know cortical neural progenitor cells are the vulnerable cells, they can likely also be used to quickly screen potential new therapies," said Song. Outside of pregnancy, Zika is normally no more threatening than a bad cold or a mild case of the flu. Evidence piling up An apparent link with microcephaly emerged as the cases of infection with the virus spread, coinciding with an increase in brain defects. In Brazil, the country apparently worst-hit, the number of confirmed and suspected cases of microcephaly associated with Zika this week rose from to 4,863 from 4,690 a week earlier. The World Health Organization (WHO) said on Friday that there was mounting evidence of a link between the virus and microcephaly, as well as the rare paralysis-causing Guillain-Barre syndrome. The WHO Emergency Committee is due to meet on Tuesday to review "evolving information" and to re-examine recommendations on travel, trade and mosquito control. http://www.dw.com/en/lab-tests-reveal-link-between-zika-and-microcephaly/a-19096257

BANGKOK: Laos is the latest country to report a local transmission of Zika virus, according to the World Health Organization, as fears mount over the mosquito-borne illness that has been linked to birth defects. Asia has seen only a sprinkling of cases of the virus, but a surge in Latin America this year has pushed the UN health agency to declare Zika a global health emergency. Laos joined a total of 41 countries that have reported local transmissions of the virus since the beginning the year, a WHO report said. Health authorities in Laos, a rural Communist country with minimal infrastructure, were not available to comment. Neighbouring Thailand reported one case last month of a 22-year-old who contracted the illness domestically and has since recovered. Thailand's health ministry urged the public not to panic, saying there have been an average of five cases per year since 2012 with no outbreaks. The sickness is carried by the Aedes aegypti mosquito, which also spreads dengue fever. It breeds in tropical areas, including Southeast Asia, which has seen a spike in cases of dengue in recent months and most often causes mild, flu-like symptoms. A growing body of evidence suggests Zika can also trigger microcephaly, a severe deformation of the brain among newborns, in babies born to mothers infected while pregnant. Brazil was first to sound the alarm on the apparent link with birth defects. It has since become the hardest hit country, with an estimated 1.5 million cases of active Zika transmission and 641 confirmed cases of microcephaly. On Friday scientists in the United States said they found the first concrete evidence of a link between the virus and the birth defect, which has so far been circumstantial. The findings may help to identify drugs to prevent or cure the Zika virus, which currently lacks a vaccine or specific treatment. - AFP/yt

Laos reports local transmission of Zika virus: WHOLaos joined a total of 41 countries that have reported local transmissions of the virus since the beginning the year, a WHO report said.Posted 05 Mar 2016 20:45 Updated 05 Mar 2016 20:50http://www.channelnewsasia.com/news/asiapacific/laos-reports-local/2576028.html PHOTOS

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Updated mayches Sequences producing significant alignments:Select:AllNone Selected:0 AlignmentsDownloadGenBankGraphicsDistance tree of resultsShow/hide columns of the table presenting sequences producing significant alignmentsSequences producing significant alignments:Select for downloading or viewing reportsDescriptionMax scoreTotal scoreQuery coverE valueIdentAccessionSelect seq gb|KU729217.2|Zika virus isolate BeH823339 polyprotein gene, complete cds1852518525100%0.0100%KU729217.2Select seq gb|KU509998.1|Zika virus strain Haiti/1225/2014, complete genome1839318393100%0.099%KU509998.1Select seq gb|KJ776791.1|Zika virus strain H/PF/2013 polyprotein gene, complete cds1839018390100%0.099%KJ776791.1Select seq gb|KU321639.1|Zika virus strain ZikaSPH2015, complete genome1838118381100%0.099%KU321639.1Select seq gb|KU729218.1|Zika virus isolate BeH828305 polyprotein gene, complete cds1837218372100%0.099%KU729218.1Select seq gb|KU707826.1|Zika virus isolate SSABR1, complete genome1837218372100%0.099%KU707826.1Select seq gb|KU527068.1|Zika virus strain Natal RGN, complete genome1837218372100%0.099%KU527068.1Select seq gb|KU365779.1|Zika virus strain BeH819966 polyprotein gene, complete cds1837218372100%0.099%KU365779.1Select seq gb|KU501217.1|Zika virus strain 8375 polyprotein gene, complete cds1835718357100%0.099%KU501217.1Select seq gb|KU365780.1|Zika virus strain BeH815744 polyprotein gene, complete cds1835718357100%0.099%KU365780.1Select seq gb|KU497555.1|Zika virus isolate Brazil-ZKV2015, complete genome183541835499%0.099%KU497555.1Select seq gb|KU647676.1|Zika virus strain MRS_OPY_Martinique_PaRi_2015 polyprotein gene, complete cds1835418354100%0.099%KU647676.1Select seq gb|KU501216.1|Zika virus strain 103344 polyprotein gene, complete cds1835418354100%0.099%KU501216.1Select seq gb|KU365777.1|Zika virus strain BeH818995 polyprotein gene, complete cds1835418354100%0.099%KU365777.1Select seq gb|KU820897.1|Zika virus isolate FLR polyprotein gene, complete cds1833918339100%0.099%KU820897.1Select seq gb|KU365778.1|Zika virus strain BeH819015 polyprotein gene, complete cds1833918339100%0.099%KU365778.1Select seq gb|KU312312.1|Zika virus isolate Z1106033 polyprotein gene, complete cds1833918339100%0.099%KU312312.1Select seq gb|KU501215.1|Zika virus strain PRVABC59, complete genome1833018330100%0.099%KU501215.1Select seq gb|KU761564.1|Zika virus isolate GDZ16001 polyprotein gene, complete cds1831218312100%0.099%KU761564.1Select seq gb|KU740184.1|Zika virus isolate GD01 polyprotein gene, complete cds1830318303100%0.099%KU740184.1Select seq gb|KU820899.1|Zika virus isolate ZJ03 polyprotein gene, complete cds1828518285100%0.099%KU820899.1Select seq gb|KU744693.1|Zika virus isolate VE_Ganxian, complete genome1814618146100%0.099%KU744693.1Select seq gb|KU681081.3|Zika virus isolate Zika virus/H.sapiens-tc/THA/2014/SV0127- 14, complete genome1804718047100%0.099%KU681081.3Select seq gb|JN860885.1|Zika virus isolate FSS13025 polyprotein gene, partial cds177391773999%0.098%JN860885.1Select seq gb|KF993678.1|Zika virus strain PLCal_ZV from Canada polyprotein gene, partial cds176941769498%0.099%KF993678.1Select seq gb|EU545988.1|Zika virus polyprotein gene, complete cds1758517585100%0.098%EU545988.1Select seq gb|KU681082.3|Zika virus isolate Zika virus/H.sapiens-tc/PHL/2012/CPC-0740, complete genome1743817438100%0.098%KU681082.3Select seq gb|HQ234499.1|Zika virus isolate P6-740 polyprotein gene, partial cds164151641599%0.095%HQ234499.1Select seq gb|KF268948.1|Zika virus isolate ARB13565 polyprotein gene, complete cds1328413284100%0.089%KF268948.1Select seq gb|KF383115.1|Zika virus strain ArB1362 polyprotein gene, complete cds1327913279100%0.089%KF383115.1Select seq gb|KF268950.1|Zika virus isolate ARB7701 polyprotein gene, complete cds1327713277100%0.089%KF268950.1Select seq gb|KF268949.1|Zika virus isolate ARB15076 polyprotein gene, complete cds1327513275100%0.089%KF268949.1Select seq gb|KU720415.1|Zika virus strain MR 766 polyprotein gene, complete cds1327213272100%0.089%KU720415.1Select seq gb|HQ234498.1|Zika virus isolate MR_766 polyprotein gene, partial cds132661326699%0.089%HQ234498.1Select seq gb|DQ859059.1|Zika virus strain MR 766 polyprotein gene, complete cds1325713257100%0.089%DQ859059.1Select seq gb|KF383119.1|Zika virus strain ArD158084 polyprotein gene, complete cds1325413254100%0.089%KF383119.1Select seq dbj|LC002520.1|Zika virus genomic RNA, complete genome, strain: MR766-NIID1325013250100%0.089%LC002520.1Select seq gb|KF383116.1|Zika virus strain ArD7117 polyprotein gene, complete cds1322113221100%0.089%KF383116.1Select seq gb|HQ234501.1|Zika virus isolate ArD_41519 polyprotein gene, partial cds132051320599%0.089%HQ234501.1Select seq gb|AY632535.2|Zika virus strain MR 766, complete genome1319113191100%0.088%AY632535.2Select seq gb|KF383117.1|Zika virus strain ArD128000 polyprotein gene, complete cds1314213142100%0.088%KF383117.1Select seq gb|HQ234500.1|Zika virus isolate IbH_30656 polyprotein gene, partial cds131351313599%0.088%HQ234500.1Select seq gb|KF383118.1|Zika virus strain ArD157995 polyprotein gene, complete cds1293112999100%0.088%KF383118.1Select seq gb|KF383121.1|Zika virus strain ArD158095 polyprotein gene, partial cds128521285297%0.089%KF383121.1Select seq gb|KF383120.1|Zika virus strain ArD142623 nonfunctional polyprotein gene, partial sequence108301083097%0.084%KF383120.1Select seq gb|KU312314.1|Zika virus isolate Z1106031 polyprotein gene, partial cds4967496727%0.099%KU312314.1Select seq gb|KU312313.1|Zika virus isolate Z1106032 polyprotein gene, partial cds4940494027%0.099%KU312313.1Select seq gb|KU646828.1|Zika virus isolate Si322 polyprotein gene, partial cds4628462825%0.099%KU646828.1Select seq gb|KU646827.1|Zika virus isolate Si323 polyprotein gene, partial cds4619461925%0.099%KU646827.1Select seq gb|KU312315.1|Zika virus isolate Z1106027 polyprotein gene, partial cds3422342218%0.099%KU312315.1Select seq gb|KU740199.1|Zika virus isolate VE_Ganxian2016 polyprotein gene, partial cds3214321417%0.099%KU740199.1Select seq gb|DQ859064.1|Spondweni virus strain SM-6 V-1 polyprotein gene, complete cds2870419795%0.071%DQ859064.1Select seq gb|KJ634273.1|Zika virus strain CK-ISL 2014 E protein (E) gene, partial cds2682268214%0.099%KJ634273.1Select seq gb|KU686218.1|Zika virus isolate MEX/InDRE/14/2015 polyprotein gene, partial cds2048204811%0.099%KU686218.1Select seq gb|KU179098.1|Zika virus isolate JMB-185 nonstructural protein 5 gene, partial cds2017201711%0.099%KU179098.1Select seq gb|KM078936.1|Zika virus strain CHI1410214 NS5 protein gene, partial cds175217529%0.099%KM078936.1Select seq gb|KM078961.1|Zika virus strain CHI2612114 NS5 protein gene, partial cds174817489%0.099%KM078961.1Select seq gb|KM078930.1|Zika virus strain CHI2283714 NS5 protein gene, partial cds174617469%0.099%KM078930.1Select seq gb|KM078971.1|Zika virus strain CHI2613014 NS5 protein gene, partial cds174517459%0.099%KM078971.1Select seq gb|KM078970.1|Zika virus strain CHI2490414 NS5 protein gene, partial cds174517459%0.099%KM078970.1Select seq gb|KM078933.1|Zika virus strain CHI1058514 NS5 protein gene, partial cds174517459%0.099%KM078933.1Select seq gb|KM078929.1|Zika virus strain CHI1805214 NS5 protein gene, partial cds174317439%0.099%KM078929.1Select seq gb|KJ873160.1|Zika virus isolate NC14-03042014-3481 nonstructural protein 5 gene, partial cds160216028%0.099%KJ873160.1Select seq gb|KJ873161.1|Zika virus isolate NC14-02042014-3220 nonstructural protein 5 gene, partial cds142014207%0.099%KJ873161.1Select seq gb|KM851039.1|Zika virus strain SV0127/14 nonstructural protein 5 gene, partial cds138213827%0.099%KM851039.1Select seq gb|KU556802.1|Zika virus isolate MEX/InDRE/14/2015 NS5 protein gene, partial cds134613467%0.099%KU556802.1Select seq gb|KM851038.1|Zika virus strain CPC-0740 nonstructural protein 5 gene, partial cds134613467%0.098%KM851038.1Select seq gb|AF013415.1|Zika virus strain MR-766 NS5 protein (NS5) gene, partial cds1306130610%0.088%AF013415.1Select seq gb|KU232300.1|Zika virus isolate 067ZV_PEBR15 NS5 protein gene, partial cds124012406%0.099%KU232300.1Select seq gb|KT200609.1|Zika virus isolate BR/949/15 NS5 gene, partial cds123612366%0.099%KT200609.1Select seq gb|KU232290.1|Zika virus isolate 036ZV_PEBR15 NS5 protein gene, partial cds123112316%0.099%KU232290.1Select seq gb|KU232297.1|Zika virus isolate 049ZV_PEBR15 NS5 protein gene, partial cds122912296%0.099%KU232297.1Select seq gb|KU232294.1|Zika virus isolate 061ZV_PEBR15 NS5 protein gene, partial cds122012206%0.099%KU232294.1Select seq gb|KU232292.1|Zika virus isolate 054ZV_PEBR15 NS5 protein gene, partial cds121812186%0.099%KU232292.1Select seq gb|KU232298.1|Zika virus isolate 050ZV_PEBR15 NS5 protein gene, partial cds121412146%0.099%KU232298.1Select seq gb|KU232296.1|Zika virus isolate 045ZV_PEBR15 NS5 protein gene, partial cds121112116%0.099%KU232296.1Select seq gb|KU232293.1|Zika virus isolate 057ZV_PEBR15 NS5 protein gene, partial cds121112116%0.099%KU232293.1Select seq gb|KU232295.1|Zika virus isolate 068ZV_PEBR15 NS5 protein gene, partial cds120512056%0.099%KU232295.1Select seq gb|KU232288.1|Zika virus isolate 001ZV_PEBR15 NS5 protein gene, partial cds119511956%0.099%KU232288.1Select seq gb|KU232289.1|Zika virus isolate 020ZV_PEBR15 NS5 protein gene, partial cds119111916%0.099%KU232289.1Select seq gb|KU232299.1|Zika virus isolate 015ZV_PEBR15 NS5 protein gene, partial cds118711876%0.099%KU232299.1Select seq gb|KU232291.1|Zika virus isolate 051ZV_PEBR15 NS5 protein gene, partial cds118611866%0.099%KU232291.1Select seq gb|KU758878.1|Zika virus polyprotein gene, partial cds113911396%0.099%KU758878.1

5 CONFIRMED CASES OF ZIKA IN NC; EXPERTS STUDYING VIRUS Researchers discuss the risks here in the US. EMBED By Stephanie LopezFriday, March 04, 2016 06:34PMCHAPEL HILL (WTVD) --There are five confirmed cases of Zika in North Carolina according to the North Carolina Department of Health and Human Services, including one case in Wake County, and there are 109 pregnant women in the state still awaiting test results from the Center for Disease Control according to UNC Health Care. Biomedical research experts at UNC said the number of cases is not high considering the amount of travelers that have areas with higher risk rates such as Central America, South America, and the Caribbean. WAKE COUNTY RESIDENT CONTRACTS ZIKA VIRUS WHILE TRAVELING OUTSIDE THE US University researchers said the risk for locally transmitted cases in the US is minimal but said the number of imported cases is something to focus on. UNC is assembling a team of experts to study the virus and its identifying markers, as there are still a lot of unanswered questions about it. "We won't be able to develop a vaccine if we can't tell who is and who isn't infected," said David Weber, associate chief medical officer at UNC Health Care. "So our first effort has to be on diagnostics, and we're very involved in that." "The second effort, which you've heard from research, is to develop more about the epidemiology - the questions you're concerned about - and so that is 'is it all phases of pregnancy? Is it only maybe weeks 12 through 14 (which we could provide better estimates to individuals)? How long can a male who is infected transmit disease? Will we find female to male transition? Are there other manifestations of Zika virus we don't know about?' " http://abc11.com/health/5-confirmed-cases-of-zika-in-nc;-experts-studying-virus/1231483/

Studies strengthen link between Zika virus, birth defectsBy Ralph Ellis, CNN Updated 0436 GMT (1236 HKT) March 5, 2016 | Video Source: CNN What is the Zika virus? Zika virus linked to birth defect in newborns Mutant mosquitos to help fight Zika virus Zika virus: Inside the CDC WHO: Zika virus 'spreading explosively' Mosquito-borne virus poses risk to pregnant women Stopping the spread of Zika virus in the U.S. Tourism industry rattled by Zika virus, terrorism Dangers of Zika virus Brazil is taking steps against the Zika virus WHO: Zika virus spreading to almost all the AmericasNow PlayingZika virus linked to birth defects in pregnant womenAmerica's first Zika patient speaks outThe world's deadliest animal is ... ?Living with the Zika virusGrowing concerns as researchers battle Zika virus Family raises two daughters with microcephaly Brazilian lab finds Zika virus in saliva, urine Zika virus tests Catholic beliefs The origin of the Zika virus Officials: U.S. Zika case sexually transmitted What is the Zika virus? Zika virus linked to birth defect in newborns Mutant mosquitos to help fight Zika virus Zika virus: Inside the CDC WHO: Zika virus 'spreading explosively' Mosquito-borne virus poses risk to pregnant women Stopping the spread of Zika virus in the U.S. Tourism industry rattled by Zika virus, terrorism Dangers of Zika virus Brazil is taking steps against the Zika virus WHO: Zika virus spreading to almost all the AmericasZika virus linked to birth defects in pregnant womenAmerica's first Zika patient speaks outThe world's deadliest animal is ... ?Living with the Zika virusGrowing concerns as researchers battle Zika virus Family raises two daughters with microcephaly Brazilian lab finds Zika virus in saliva, urine Zika virus tests Catholic beliefs The origin of the Zika virus Officials: U.S. Zika case sexually transmitted What is the Zika virus? Story highlightsOne study says the virus appears to selectively infect cells in the brain's outer layerSecond study says ultrasounds found fetal abnormalities in 29% of women infected with Zika virus (CNN)Scientists have long thought the Zika virus caused birth defects such as microcephaly, a condition in which a baby is born with a small head. That belief was bolstered Friday by two studies published in medical journals. Researchers working with lab-grown human stem cells "suspect they have discovered how the Zika virus probably causes microcephaly in fetuses," reported the journal Cell Stem Cell. The researchers, working in the laboratory, determined the Zika virus selectively infects cells in the brain's cortex, or outer layer, making those cells "more likely to die and less likely to divide normally and make new brain cells," according to a press release from the journal. While bolstering the connection between Zika virus and brain defects in babies, one of the researchers cautioned that it doesn't establish a conclusive link. Disease detectives hunt for Zika-microcephaly connection in Brazil "While the study doesn't definitely prove that Zika virus causes microcephaly, it's very telling that the cells that form the cortex are potentially susceptible to the virus and their growth could be disrupted by the virus," said Dr. Guo-li Ming, a professor at Johns Hopkins' Institute for Cell Engineering. These lab-grown cells might be used to screen for drugs that protect the cells, Cell Stem Cell said. Meanwhile, the New England Journal of Medicine reported on research conducted on 88 pregnant women in Rio de Janerio, one of the nations suffering most from the Zika virus. The scientists concluded that Zika infection during pregnancy has "grave outcomes, including fetal death, placental insufficiency, fetal growth, restriction, and [central nervous system] involvement," the journal said. 5 things to know about the Zika virus The study said blood and urine tests found 72 of the 88 women had the Zika virus. Of the 42 infected women who had ultrasounds, major fetal abnormalities were found in 12 of them -- nearly a third. The abnormalities included microcephaly, calcification of the brain, abnormal flow of amniotic fluid, abnormal flow of blood to the brain and fetal deaths, the study said. "In summary, we believe that our findings provide further support for a link between maternal Zika infection and fetal and placental abnormalities that is not unlike that of other viruses that are known to cause congenital infections," the study said. Also on Friday, the World Health Organization released a situation report on Zika. The main points of the report: --Since January 2015, 41 countries and territories have reported Zika virus transmission. --Thirty-one of these countries and territories are in the Americas. --Increases in microcephaly and other neonatal malformations have been reported in Brazil and French Polynesia. --Increases in Guillain-Barré syndrome linked to Zika have been reported in eight countries and territories. The Zika virus is a flavivirus, part of the same family as yellow fever, West Nile, chikungunya and dengue. But unlike some of those viruses, there is no vaccine to prevent Zika or medicine to treat the infection. CNN's Debra Goldschmidt contributed to this report. http://edition.cnn.com/2016/03/04/health/zika-virus-and-birth-defects/index.html?eref=edition

Zika has spread to more than 50 countries and territories, but so far officials have said that only one country has experienced a spike of the birth defect microcephaly linked to Zika. (AP Photo) WHO reticent to confirm Zika-birth defect link By ROBERT KING • 3/5/16 12:01 AMSHARETWEETMailPrintMore Evidence is mounting that the Zika virus causes a debilitating birth defect, but the World Health Organization is not prepared to confirm such a link. Zika has spread to more than 50 countries and territories, but so far officials have said that only one country has experienced a spike of the birth defect microcephaly linked to Zika. That country is Brazil, which was the first to be affected by the outbreak that started last spring. The World Health Organization said Friday that it will be "some months" before a link can be proven between Zika and microcephaly, which causes babies to be born with abnormally small heads and brain damage. More from the Washington ExaminerHow Donald Trump played the mediaBy Eddie Scarry • 03/05/16 12:01 AM Uber: a route out of the French banlieues.Baba likes to say Uber got him out of jail – and kept him out. His story is one of many driver-partners in France.PROMOTED BY UBER "Microcephaly is a pregnancy outcome, probably associated most with first trimester exposure [to Zika] if indeed that relationship is causal," Bruce Aylward, executive director for Outbreaks and Health Emergencies at the WHO, said during a Friday press conference. A recent small study is the latest to find evidence of a link between Zika and microcephaly. The New England Journal of Medicine published a study Friday that followed 88 women from September 2015 to February 2016, about 72 of whom tested positive for Zika. The women got infected between five-38 weeks of pregnancy. Researchers performed an ultrasound on 42 Zika-positive women and in all Zika-negative women. The ultrasounds were taken at different parts of the pregnancy, including between 20-30 weeks and after 30 weeks. Fetal abnormalities were found in 12 of the 42 Zika-positive women and none of the other women. Eight of the 42 women have delivered their babies, and the ultrasound findings were confirmed, the study said. Also from the Washington ExaminerSanders campaign pushes back against middle class tax hike chargeBy Joseph Lawler • 03/04/16 11:52 PMAbnormalities included not just microcephaly, but other defects such as far too much fluid in the brain and fetuses that were very small. The researchers behind the study said women with suspected or confirmed Zika infection need to be monitored very closely and have frequent ultrasounds. "The establishment of a scientifically credible link between [Zika] and abnormal congenital findings is of utmost importance for the effective and successful management of this epidemic in Brazil and worldwide," the study said. The study was released on the same day as another finding that scientists discovered a potential link in how Zika affects pregnancies. But so far the WHO said that Zika-linked cases of microcephaly were found only in Brazil and French Polynesia, which experienced an outbreak back in 2013-14. The spike in that country was found after the outbreak subsided. http://www.washingtonexaminer.com/who-reticent-to-confirm-zika-birth-defect-link/article/2585008?custom_click=rss

First Likely Microcephalic Babies Born In ColombiaThis sure puts a dent in those conspiracy theories. 03/04/2016 05:30 pm ET Anna AlmendralaSenior Healthy Living EditorGLOW WELLNESS VIA GETTY IMAGESThree Colombian newborns could be the country’s first group of children with Zika virus-linked brain abnormalities -- a sign of what's to come as pregnant Colombian women infected with the virus begin to give birth. The babies were born with either microcephaly, which is a birth defect characterized by an abnormally small head, or congenital brain abnormalities, according to a news site run by the international science journal Nature. All three children also tested positive for Zika virus, a mosquito-borne disease that usually produces mild symptoms in adults but is believed to adversely affect fetuses andcause neurological issues in some adults. Zika virus has been spreading through the Americas since 2015. The Colombian Collaborative Network on Zika, the group of researchers that diagnosed the children, is also investigating several more possible cases of microcephaly with a suspected link to Zika, Nature reported. Colombians first started testing positive for Zika in October, months after the current outbreak took hold in Brazil. Now an estimated 37,000 Colombians have had the virus, including more than 6,000 pregnant women. This makes Colombia the second-most Zika-affected country after Brazil, which has seen an estimated 498,000 to 1.5 million cases. Experts predict that by June, Colombia will see a large increase in babies born with microcephaly. As part of the effort to determine if Zika virus causes microcephaly, Colombian officials are watching 2,000 of the country's pregnant women to see how their pregnancies and births proceed. The outcomes for the three babies detailed in Nature puts a major dent in a central argument made by conspiracy theorists and doctors who are skeptical about the causal link between Zika and microcephaly. These skeptics have pointed to Colombia -- a country that has tens of thousands of people infected with Zika virus but had no previously confirmed related cases of microcephaly -- as evidence that Zika may not be behind the uptick in severe brain defects in babies reported in Brazil, where authorities have confirmed microcephaly in 641 children and are still investigating 4,222 cases. One fact the conspiracy theorists had not accounted for is that microcephaly can't be detected in ultrasounds until very late in the pregnancy, which may be one reason why Colombia had not seen any cases until now. While scientists can't yet definitively say that Zika virus causes microcephaly, research to date on the link between the disease and the birth defects is highly suggestive. Lab studies have located Zika virus in the brain tissues and amniotic fluid of microcephalic fetuses and newborns, while population studies find microcephalic children in areas of Brazil that have recorded the highest Zika virus cases. New in vitro studies that observed how the original Zika virus strain interacts with different kinds of stem cells found that the virus is especially adept at infecting brain stem cells, reports the Atlantic. These stem cells then reproduced Zika virus at their own expense, which lead to more virus and less brain cells. The case studies of the three newborns come a few weeks after Colombia reported a “probable” case of microcephaly in an aborted fetus. Because its remains were improperly discarded, health officials could not confirm the initial microcephaly diagnosis, nor could they test tissues for presence of the Zika virus. However, traces of the virus were found in the amniotic fluid. The World Health Organization declared Brazil's cluster of microcephaly cases and their suspected link to Zika virus to be a Public Health Emergency of International Concern, and is coordinating efforts to research whether or not the disease causes birth defects. http://www.huffingtonpost.com/entry/colombia-sees-first-microcephalic-births-linked-to-zika-virus_us_56d9d87fe4b03a4056787c29

Seventh Case Of Zika Virus Reported In Illinois: Health OfficialsMarch 4, 2016 4:22 PMFiled Under: Illinois, Zika 8(CBS) — The state of Illinois has confirmed a new case of the Zika virus. Seven cases of Zika virus are now confirmed by the Illinois Department of Public Health. We know that at least one of those cases is in Chicago. The state Department of Public Health says two of the cases are inpregnant women. Three are in non-pregnant women. Two are men. The Zika virus can be sexually transmitted. But in these cases, state health officials say all seven people had traveled to countries, where mosquitoes are the more common means of transmission. They include Colombia, El Salvador, Barbados, Honduras, Puerto Rico – and two of the Illinois Zika cases had been in Haiti. http://chicago.cbslocal.com/2016/03/04/seventh-case-of-zika-virus-reported-in-illinois-health-officials/

Zika 'guilty until proven innocent,' new studies showThe mosquito-borne virus may cause microcephaly and other negative outcomes during all stages of pregnancy.Share on Facebook UESLEI MARCELINO / REUTERS A study in Brazil showed a higher-than-usual rate of abnormalities in ultrasounds of pregnant women. Of 42 women who had the exam, 29 per cent had abnormal results. The norm is 1 or 2 per cent. By: Jennifer Yang Global health reporter, Published on Fri Mar 04 2016Two new studies provide “frightening and sobering” evidence that the Zika virus may be causing not just microcephaly but other negative outcomes during all stages of pregnancy, from fetal death to potential blindness caused by damage to the central nervous system. The papers, published by the New England Journal of Medicineand Cell Stem Cell, were both published online Friday, hours after the World Health Organization announced an emergency committee meeting next week to review “accumulating evidence” linking Zika with serious neurological disorders. It will be the second such meeting since the WHO first declared a public health emergency over Zika’s worrying link to the autoimmune disorder Guillain-Barré syndrome and microcephaly, a birth defect associated with abnormally small brains and developmental delays. Zika’s culpability has yet to be definitively proven —proof is probably months or years away — but these latest studies lend further support to the WHO’s position that Zika is “guilty until proven innocent.” “The evidence has now become very compelling and I think it’s urgent to continue to study this very aggressively,” said Dr. Mark Schleiss, director of pediatric infectious diseases and immunology at the University of Minnesota Medical School, who was not involved with either study. Schleiss said study reported in Cell Stem Cell is a “very, very important paper,” demonstrating that Zika can kill brain cells while offering a framework for understanding how the virus might be causing microcephaly. The NEJM research, which followed 88 pregnant women in Brazil, provided “a rather frightening and sobering” perspective, showing that out of 42 women who had an ultrasound exam, 29 per cent had abnormal results. “The risk is really probably much higher, as reported in this paper, than what any of us would’ve predicted,” Schleiss said. “So we may just now be seeing the beginning of an increasing epidemic with even more cases. It is very sobering.” In the Cell Stem Cell paper, U.S. researchers used lab-grown human stem cells to show that Zika can infect cells that form the brain’s cortex. Infected cells were then more likely to die and less likely to divide normally.“We’re literally the first people in the world to know this, to know that this virus can infect these very important cells and interfere with their function,” said lead author,Hengli Tang, a virologist with Florida State University.The NEJM paper, on the other hand, is the first “prospective cohort study” of Zika and newborn malformations — meaning U.S. and Brazilian researchers enrolled a group of women and followed them over the course of their pregnancies. The 88 pregnant women included in the study all developed a rash within five days of being treated by a clinic with the Oswaldo Cruz Foundation in Rio de Janeiro. Seventy-two had blood or urine samples that tested positive for Zika virus between September 2015 and mid-February. Of the 42 women who consented to ultrasound exams, 29 per cent had abnormal results, according to senior author Dr. Karin Nielsen, a professor and infectious pediatric disease expert with UCLA’s David Geffen School of Medicine. “In a healthy population, it’s usually around 1 per cent or 2 per cent at most,” she said. By comparison, all 16 women who were not infected by Zika had normal ultrasounds. The abnormal results included not just microcephaly but also “intrauterine growth restrictions” and brain malformations. Of the eight babies born so far, two were stillborn and three have microcephaly or brain calcifications, according to Nielsen. Two also suffer from retinal impairment, indicating they will probably suffer from vision problems. Nielsen was surprised that even women infected during their third trimester experienced serious outcomes, including stillbirths and one baby at 40 weeks who had no amniotic fluid. “Zika seems to be a problem when there is an infection in women in any trimester of pregnancy,” she said. “They’re not out of the woods just because the first trimester is over.” Nielsen said Brazil is now suffering a “perfect storm” because this surge in microcephaly is converging with a struggling economy and failure to control the mosquito that spreads Zika. “This will be a big burden on the country,” she said. “Children with brain disorders are very expensive to follow and to maintain, and need a lot of services.” According to the WHO, only two countries have reported an increase in microcephaly cases during a Zika outbreak so far: Brazil and French Polynesia, which suffered an outbreak in 2013 and 2014. But this week news reports indicated that Colombian scientists have confirmed their first cases of birth defects associated with Zika. A large prospective study involving roughly 5,000 pregnant women, mostly in Colombia, is still underway, however, and final results probably won’t be available until June, according to WHO. http://www.thestar.com/news/world/2016/03/04/zika-guilty-until-proven-innocent-new-studies-show.html

ZIKA VIRUS OUTBREAKMAR 4 2016, 6:38 PM ETStudy Finds Zika Damages Babies at All Stages of Pregnancyby MAGGIE FOX Gleyse Kelly holds her daugther Maria Geovana, in Recife, Brazil UESLEI MARCELINO / Reuters SHAREShareTweetShareEmailPrintCommentThe babies of women infected with Zika virus while they are pregnant can suffer the effects at any stage of gestation, researchers reported Friday in a troubling look at how Zika affects unborn children. Two babies died just before they should have been born after their mothers became infected, the international team found. They also found the virus causes a range of birth defects beyond microcephaly. They suggest a name for these effects: Zika virus congenital syndrome. Babies have been born with a range of brain and eye defects and some have also been abnormally small. The findings, together with other studies, support what most experts already believe: that Zika is causing an epidemic of birth defects. Earlier Friday, a different team reported that tests in lab dishes show that Zika goes straight into developing brain cells and turns them into virus factories before killing them. And the findings strongly support the idea that Zika, a once-obscure virus believed to cause little more than a headache and a rash, can be a killer. "Despite mild clinical symptoms, Zika virus infection during pregnancy appears to be associated with grave outcomes, including fetal death, placental insufficiency, fetal growth restriction and central nervous system injury," they wrote in their report, published in the New England Journal of Medicine. "THERE'S MORE THAN MICROCEPHALY. THERE IS A SPECTRUM OF DISEASE.""We saw problems with the fetus or the pregnancy at eight weeks, 22 weeks, 25 weeks, and we saw problems at 35 weeks," said Dr. Karin Nielsen, professor of clinical pediatrics at the David Geffen School of Medicine at the University of California Los Angeles, who helped organize the study. "Even if the fetus isn't affected the virus appears to damage the placenta, which can lead to fetal death," Nielsen said. Two babies died just days before they were due. Related: Zika Can Cause Eye Defects "Any woman with Zika virus should be handled as a high-risk pregnancy," Nielsen told NBC News. "There's more than microcephaly. There is a spectrum of disease. There are parts of the brain that are not formed. There are calcifications in the brain. There is in-utero growth restriction." Many of the symptoms are similar to what's been seen when women get rubella while pregnant, including microcephaly, marked by a smaller than normal brain and head. Children who survive birth with microcephaly can grow up with often profound physical and mental disabilities. Calcifications are hardened remnants of dead tissue. Other studies have shown that Zika in the brains of some babies miscarried or aborted after a mother was infected. Related: Two Cases Link Zika to Paralyzing Condition Nielsen was working with Dr. Patricia Brasil and colleagues at the Oswaldo Cruz Foundation in Rio de Janeiro. They were already running a study of dengue virus, asking pregnant women to come in and be tested if they showed symptoms of dengue, such as a rash. Dengue is related to Zika and it's spread by the same mosquitoes, the Aedes aegypti mosquitoes that spread Zika. And like Zika, dengue is spreading fast across Brazil and other Latin American countries. So Nielsen's team was up and running when Zika started causing alarm. They tested blood and urine from 88 women between September and February. More than 80 percent of the women with symptoms such as fever and rash tested positive for Zika in the blood, urine or both. The women were at various stages of pregnancy. Nielsen's team was able to follow them in real time to see what happened to their pregnancies. They found 29 percent of the fetuses had some sort of problem, from brain damage to damage to the placenta. "ONE IMPORTANT FINDING WAS THAT THERE WERE PROBLEMS WITH PREGNANCY IN THE THIRD TRIMESTER AS WELL, WHICH WAS SURPRISING TO US."Nielsen's study is the first to show what happens from the time a woman becomes infected. That can answer one big question: when the most dangerous time of pregnancy is. "We know when the infection is taking place," she said. "We can associate that with weeks of gestation, so we can know if there are any malformations, what time they happened — we can associate them with a first trimester, second trimester and third trimester infection." The answers are not reassuring. The experts have predicted that the first trimester would be the most dangerous time for a fetus if a woman became infected. But Nielsen's team found babies were hurt even late in pregnancy. "One important finding was that there were problems with pregnancy in the third trimester as well, which was surprising to us," she said. Some had looked normal on ultrasound, even, before they died in the womb. "It is not normal to find two fetal deaths that late in pregnancy in that small a group of women," she said. Related: CDC Confirms 9 Zika Pregnancies in U.S. The team is studying the babies to see if they can find out why they died. And they're watching the rest of the pregnant women to see what happens. World Health Organization and Brazilian health officials are worried. They've seen more than 4,000 cases of microcephaly in recent months, and more than a million people have been infected. Colombia, the second Latin American country to get hit with Zika, has started to report Zika-linked cases of microcephaly. "This virus hit in a perfect storm," Nielsen said. "You are talking about a very large population in Brazil. When you have a lot of people infected, you are going to see problems." http://www.nbcnews.com/storyline/zika-virus-outbreak/study-finds-zika-damages-babies-all-stages-pregnancy-n532086

Breakthrough Study Shows Strong Link Between Zika Virus, Severe Birth Defects By: Beth Galvin POSTED:MAR 04 2016 05:30PM EST UPDATED:MAR 04 2016 05:30PM EST ATLANTA, Ga. -There is still no direct confirmation Zika virus, spread by infected mosquitoes, is to blame more than 5,600 Brazilian babies born with abnormally small heads. But the CDC and other health organizations say the evidence of a link between Zika and microcephaly is growing. The Atlanta-based agency is warning pregnant women to avoid more than 30 areas where the Zika virus is actively spreading. Now a chilling new study, conducted by both American and Brazilian researchers, is driving home that warning. The team followed 88 woman at a clinic in Rio de Janeiro. The researchers found when a pregnant women is infected and becomes symptomatic, there is a good chance the virus could do serious damage to her unborn baby. The study found 29% percent of pregnant women given ultrasounds after testing positive for Zika virus had fetuses that suffered "grave outcomes," including fetal death and nerve damage that can lead to blindness. And the virus may pose a threat not just in the first trimester, but throughout a woman’s pregnancy. Two women in the Brazil study, infected at 25 and 32 weeks gestation, lost their pregnancies, even though their previous ultrasounds prior to their infections were normal. The study was published in the online version of The New England Journal of Medicine. In another research study, published in the journal Cell Stem Cell, researchers say they may have a better understanding of how the virus may damage the developing brain. They found Zika virus may directly target fetal brain cells, disrupting normal brain development. Working quickly, they say, the virus infects the cells and causes them to die off. Then, it uses those damaged brain cells to reproduce itself and infect more cells. http://www.fox5atlanta.com/health/fox-medical-team/100654678-story

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Mo. man diagnosed with Zika virusBailey E Kinney, KSDK 4:17 PM. CST March 04, 20161(Photo: Thinkstock/jarun011, Custom) CONNECT TWEET LINKEDIN GOOGLE+ PINTERESTA Missouri man, who recently traveled to Haiti, has been positively diagnosed with the Zika virus. This is the first confirmed case of the Zika virus infection in a resident of Missouri. The majority of people who contract the virus don't exhibit symptoms, but those that do can expect a fever, rash, joint soreness and/or reddened eyes. According to the CDC, the virus is most commonly spread through mosquito bites, but has also been transmitted through unprotected sexual contact, blood transfusions and infected pregnant moms can spread the virus to their unborn babies. No vaccines currently exist to prevent the virus so people are encouraged to avoid mosquito bites in affected areas. No cases of infection from mosquito bites have been reported in Missouri. http://www.ksdk.com/news/local/mo-man-diagnosed-with-zika-virus/68059190

A Missouri man, who recently traveled to Haiti, has been positively diagnosed with the Zika virus. This is the first confirmed case of the Zika virus infection in a resident of Missouri. http://www.ksdk.com/news/local/mo-man-diagnosed-with-zika-virus/68059190

Study provides 'strongest evidence yet' linking Zika, birth defects Liz Szabo, USA TODAY5:04 p.m. EST March 4, 2016(Photo: Andre Penner, AP) CONNECTTWEETLINKEDINCOMMENTEMAILMOREA new study provides the strongest evidence yet that the Zika virus is the cause of devastating birth defects seen in Brazil, home to the largest outbreak of the disease. Authors of the new study have followed 88 pregnant women in Brazil to see whether being infected with Zika, which is spread by mosquitoes, increases the rate of birth defects. Seventy-two of the women tested positive for the virus. The women's blood and urine were tested five days or less after they developed an itchy rash, a tell-tale symptom of Zika. Other symptoms of Zika infection included fever, pink eye, swollen lymph nodes and joint pain. Most people with Zika have no symptoms. Ultrasounds found major abnormalities in 29% of the fetuses from women who tested positive for Zika, but none of the women without Zika infections, according to the study, published online Friday in The New England Journal of Medicine. Women were exposed to the Zika virus between the sixth and 35th week of pregnancy. A typical pregnancy lasts 40 weeks. Those abnormalities included microcephaly, in which babies are born with unusually small skulls, which typically signifies incomplete brain development; restricted growth in the womb; poor development of brain structures; calcifications in the brain, which signal places where tissue has died; abnormal amniotic fluid levels; or abnormal blood flow in the fetal brain, umbilical cord or placenta, according to the study. "Even if the fetus isn’t affected, the virus appears to damage the placenta, which can lead to fetal death," said study senior author Karin Nielsen, a professor of clinical pediatrics in the division of pediatric infectious diseases at the David Geffen School of Medicine at UCLA. Two women with Zika infections miscarried early in pregnancy, according to the study, led by doctors at the UCLA and Fiocruz, also known as the Oswaldo Cruz Foundation, a large biomedical institute in Rio de Janeiro. Two of the babies were stillborn, dying at 36 weeks and 38 weeks, according to the study. Six women have given birth so far. Doctors plan to follow the remaining women through the end of their pregnancies and beyond, Nielsen said. Two of the babies were born small for their gestational age. One was born with severe microcephaly and eye lesions that could indicate blindness, according to the study. Doctors delivered one baby by emergency C-section because there was no amniotic fluid left in the uterus, a potentially life-threatening problem. The baby, a boy, recovered and appears to be healthy. His mother was infected with Zika in her 35th week of pregnancy. Two infants of mothers with normal ultrasound results appear to be healthy, according to the study. Ultrasound results were shown to be accurate for the two stillbirths and the six babies born alive, according to the study. "We're seeing a spectrum of abnormalities," said Nielsen, who referred to the baby's conditions as Zika Virus Congenital Syndrome. "It's not all just microcephaly." All of the mothers in the study were healthy, with no other risk factors for pregnancy complications. Babies will need hearing and vision tests, Nielsen said. http://www.usatoday.com/story/news/2016/03/04/study-provides-strongest-evidence-yet-linking-zika-birth-defects/81318418/

Study Finds Multiple Problems In Fetuses Exposed To Zika VirusUpdated March 4, 20164:53 PM ETPublished March 4, 20164:33 PM ETROB STEINTwitter Facebook Audio for this story from All Things Considered will be available at approximately 7:00 p.m. ET. iScientists are trying to figure out how Zika virus may be affecting fetuses. Felipe Dana/APThe Zika virus has sparked international alarm largely because of fears that the pathogen is causing microcephaly, a condition in which babies are born with unusually small heads and damaged brains. But the preliminary results of a study released Friday suggest Zika can also cause other potentially grave complications among fetuses being carried by women who get infected when they are pregnant. "There seems to be a whole spectrum of conditions that are related to this — not only microcephaly," says Karin Nielsen-Saines, a professor of clinical pediatrics at the David Geffen School of Medicine at UCLA who led the study. The analysis, based on the first 42 women in a larger ongoing study, found that Zika appears to increase the risk for miscarriages, poorly developed placentas, low or no amniotic fluid, severe growth problems, other kinds of brain damage, blindness and deafness, according to a preliminary report published in the New England Journal of Medicine. The results "make a very strong case for Zika virus being the cause of all these pregnancy outcomes that are not very good," Nielsen-Saines says. She cautions, however, that the study is still small and needs to be confirmed by following many more women for longer periods of time. The link between Zika and microcephaly remains largely circumstantial. It's based on the observation that the number of cases of microcephaly appear to have increased in Brazil after the virus became epidemic in that country. Researchers have also found evidence of Zika in the brains of a handful of babies with microcephaly who died shortly after birth. Concern about a possible link sparked a rush of studies to test the possibility, as well as explore whether the virus is causing other problems. The new results mark the first from a prospective study, which involves tracking the health of women who are infected with Zika and comparing them to very similar people who are not infected. "The take-home message is that this is another important addition to the growing evidence that seems to now be quite compelling of the relationship between infection of a pregnant women and the development of congenital abnormalities," says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. For the study, Nielsen-Saines and colleagues from Brazil identified 88 women in the Rio de Janeiro area who had symptoms of Zika when they were pregnant. Seventy-two of the women had their Zika infection confirmed by polymerase-chain reaction (PCR) testing, which can identify genetic material from the virus. Forty-two of those women, as well as 16 women who did not test positive for Zika, underwent ultrasounds to examine their fetuses. The ultrasounds of 12 of the infected women — 29 percent — found abnormalities. None of the Zika-negative women's ultrasounds found any problems. Five of the fetuses being carried by the Zika-infected women were not growing normally; seven had central nervous system abnormalities; and seven had abnormalities in amniotic fluid volume or blood flow. In some cases, placentas didn't seem to be developing normally. The problems observed on the ultrasounds are being explored and confirmed as the babies are being born. For example, two of the children have lesions in their retinas, Nielsen-Saines says, which means they might be blind. And she said that some may be deaf. Two were born extremely small, which means they could experience complications of low birth weight. One baby was born with microcephaly. And some of the babies are not making it to birth. There were two miscarriages early in the pregnancies, and two stillbirths just a few weeks before the babies were due, Nielsen-Saines says. Other experts say the results are alarming, given the scope of the Zika outbreak. "Millions are being affected as the epidemic has spread throughout the Americas," says Albert Ko, a professor of epidemiology at the Yale School of Public Health, who is studying Zika in Brazil. So, yes, I think this is very disturbing." http://www.npr.org/sections/health-shots/2016/03/04/469179452/study-finds-multiple-problems-in-fetuses-exposed-to-zika-virus

REFERENCES 1 Campos GS, Bandeira AC, Sardi SI. Zika virus outbreak, Bahia, Brazil. Emerg Infect Dis2015;21:1885-1886 CrossRef | Web of Science | Medline 2 Zanluca C, de Melo VC, Mosimann AL, Dos Santos GI, Dos Santos CN, Luz K. First report of autochthonous transmission of Zika virus in Brazil. Mem Inst Oswaldo Cruz2015;110:569-572 CrossRef | Web of Science | Medline 3 Musso D. Zika virus transmission from French Polynesia to Brazil. Emerg Infect Dis2015;21:1887-1887 CrossRef | Web of Science | Medline 4 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 5 Ventura CV, Maia M, Bravo-Filho V, Góis AL, Belfort R Jr. Zika virus in Brazil and macular atrophy in a child with microcephaly. Lancet 2016;387:228-228 CrossRef | Web of Science | Medline 6 Possible association between Zika virus infection and microcephaly — Brazil, 2015.MMWR Morb Mortal Wkly Rep 2016;65:59-62 CrossRef | Web of Science | Medline 7 Calvet G, Aguiar RS, Melo AS, et al. Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. Lancet Infect Dis2016 February 17 (Epub ahead of print) Medline 8 Mlakar J, Korva M, Tul N, et al. Zika virus associated with microcephaly. N Engl J Med. DOI: 10.1056/NEJMoa1600651. 9 Calvet GA, Filippis AM, Mendonça MC, et al. First detection of autochthonous Zika virus transmission in a HIV-infected patient in Rio de Janeiro, Brazil. J Clin Virol 2016;74:1-3 CrossRef | Web of Science | Medline 10 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 11 Ebbing C, Rasmussen S, Kiserud T. Middle cerebral artery blood flow velocities and pulsatility index and the cerebroplacental pulsatility ratio: longitudinal reference ranges and terms for serial measurements. Ultrasound Obstet Gynecol 2007;30:287-296 CrossRef | Web of Science | Medline 12 Gardosi J, Chang A, Kalyan B, Sahota D, Symonds EM. Customised antenatal growth charts. Lancet 1992;339:283-287 CrossRef | Web of Science | Medline 13 Tarrant A, Garel C, Germanaud D, et al. Microcephaly: a radiological review. Pediatr Radiol2009;39:772-780 CrossRef | Web of Science | Medline 14 Castanha PM, Cordeiro MT, Martelli CM, Souza WV, Marques ET Jr, Braga C. Force of infection of dengue serotypes in a population-based study in the northeast of Brazil.Epidemiol Infect 2013;141:1080-1088 CrossRef | Web of Science | Medline 15 Gourinat AC, O’Connor O, Calvez E, Goarant C, Dupont-Rouzeyrol M. Detection of Zika virus in urine. Emerg Infect Dis 2015;21:84-86 CrossRef | Web of Science | Medline 16 Epidemiological alert: neurological syndrome, congenital malformations, and Zika virus infection — implications for public health in the Americas. Washington, DC: Pan American Health Organization, December 1, 2015. 17 Butler D. Zika virus: Brazil’s surge in small-headed babies questioned by report. Nature2016;530:13-14 CrossRef | Medline 18 Calvet GA, João EC, Nielsen-Saines K, et al. Trends in a cohort of HIV-infected pregnant women in Rio de Janeiro, 1996-2004. Rev Bras Epidemiol 2007;10:323-337 CrossRef 19 Naeye RL, Blanc W. Pathogenesis of congenital rubella. JAMA 1965;194:1277-1283 CrossRef | Web of Science | Medline 20 Plotkin SA, Boue A, Boue JG. The in vitro growth of rubella virus in human embryo cells.Am J Epidemiol 1965;81:71-85 Web of Science | Medline 21 Sever JL, Schiff GM, Huebner RJ. Frequency of rubella antibody among pregnant women and other human and animal populations: a report from the Collaborative Study of Cerebral Palsy. Obstet Gynecol 1964;23:153-159 Web of Science | Medline

DISCUSSIONZIKV is a flavivirus that was recently introduced into Brazil. Its rapid expansion into a population that is probably fully susceptible is due to the effectiveness of its vector, the Aedes aegyptimosquito. Diagnosis of ZIKV infection in Brazil has been complicated by the cross-reactivity between flavivirus antibodies and by the fact that dengue has been endemic in Brazil for more than 30 years. Serosurveillance studies have found evidence of dengue antibodies in more than 90% of the population of Recife.14 In our cohort, dengue IgG antibodies were present in 88% of the women. The diagnosis of ZIKV in Brazil relies on identification of the virus through RT-PCR during the acute period of infection. The virus is detectable in blood during the period of acute viremia and initial symptoms and subsequently is shed in the urine, generally for 3 to 14 days.15 Because RT-PCR assays for ZIKV are generally not available, most cases of ZIKV infection in Brazil are diagnosed clinically, without laboratory confirmation. In our cohort, all 72 women who were positive for ZIKV had acute infection with virus that was detected in blood, urine, or both. As compared with women who tested negative for acute ZIKV infection, women who tested positive for the virus had distinctive clinical features of ZIKV infection that included conjunctival injection, lymphadenopathy, and absence of respiratory symptoms. These clinical features, in addition to a macular or maculopapular rash with pruritus, should raise the suspicion for ZIKV infection. Low-grade fever was found in only 28% of the women; therefore a case definition that is based on the presence of fever would miss more than 70% of cases.16 Whether sexual transmission of ZIKV played a role in transmission to pregnant women in our cohort is difficult to assess, since couples usually cohabitate and would presumably have the same type of vector exposure. ZIKV-positive women more frequently had a history of a symptomatic partner than did ZIKV-negative women; however, this could also be due to less exposure to the vector among uninfected couples. Links between the current ZIKV epidemic in Brazil and the rise in the number of observed cases of neonatal microcephaly have been discussed in both the scientific literature and the lay press and have generated considerable debate about whether the observed phenomenon is real, and, if so, whether microcephaly is a direct effect of ZIKV or whether it could be due to potential environmental exposure of pregnant women to teratogenic agents.17 Ultrasonographic findings in our cohort showed serious and frequent problems in fetal and central nervous system development, affecting 29% of the 42 women whose fetuses were evaluated by ultrasonography. Abnormalities were noted in the fetuses of women who were infected at any week of gestation. Fetuses infected in the first trimester had findings suggestive of pathologic change during embryogenesis, but CNS abnormalities were also seen in fetuses infected as late as 27 weeks of gestation. Findings suggestive of placental insufficiency were identified in fetuses with intrauterine growth restriction and infections occurring at later gestational ages. There were two cases of late fetal death. Microcephaly as detected by ultrasonography and confirmed at birth was noted, but in only one case was it an isolated finding that was not present in conjunction with intrauterine growth restriction. Microcephaly in our cohort was mainly part of an overall composite of restricted fetal growth and not an asymmetric, isolated finding. Although microcephaly has been widely discussed in relation to ZIKV infection in Brazil, it is important to note that other findings such as cerebral calcifications and intrauterine growth restriction were frequently present. Our findings are worrisome because 29% of ultrasonograms showed abnormalities, including intrauterine growth restriction, CNS findings, and fetal death, in fetuses of women with PCR-positive ZIKV infection. These were all healthy women with no other risk factors for adverse pregnancy outcomes. In a prior study of 662 pregnancies in HIV-infected women who were followed for 9 years in Rio de Janeiro, we noted a stillbirth rate of 2.5% and 13 mild-to-moderate infant malformations (2%), none of which occurred more than once.18 In the present scenario, over a period of a few months, we identified a fetal death rate of 4.8% — nearly twice the rate in an HIV-infected pregnant cohort followed for a decade — in addition to the serious fetal developmental problems. To date six live births have occurred: two infants with normal ultrasonographic results had normal measures and normal examinations at birth; one infant had severe microcephaly and global cerebral atrophy as identified prenatally; two infants with growth restriction in utero were found to be small for gestational age at delivery with proportionally small heads, and one infant with anhydramnios was found to have normal measures at birth. Our findings point to a link between ZIKV and abnormal fetal and placental development or placental insufficiency in a subgroup of ZIKV-positive women in whom fetal ultrasonography was performed. None of the 16 women who tested negative for acute ZIKV infection had abnormal results on fetal ultrasonography. Although the size of our control group was small and the ZIKV-negative women presumably had alternative processes for their rash, these women lived in the same geographic area as ZIKV-positive women and are likely to have had environmental exposures that were similar to those of ZIKV-positive women. Our observations suggest that many aspects of ZIKV infection are similar to those of rubella, particularly rash, arthralgias, pruritus, and lymphadenopathy in the mother without high fever. About 85% of babies with congenital rubella in the U.S. pandemic of 1959–1965 had intrauterine growth restriction.19 In congenital rubella, specific organs are small because they have a subnormal number of cells, but the cytoplasmic mass of individual cells is within normal limits 19,20; in contrast, in intrauterine growth restriction due to maternal malnutrition, for example, the number of cells is normal but the cells contain less cytoplasm. A major difference of concern between ZIKV infections in Brazil in 2015–2016 and rubella virus infections in the U.S. pandemic of 1959–1965 is the level of population immunity. In Brazil in 2015–2016, none of the population has antibodies to ZIKV. In contrast, in the United States during the rubella epidemic, there were 20,000 cases of the congenital rubella syndrome, but in 1959 only 17.5% of women of childbearing age lacked rubella antibodies.21 In summary, we believe that our findings provide further support for a link between maternal ZIKV infection and fetal and placental abnormalities that is not unlike that of other viruses that are known to cause congenital infections characterized by intrauterine growth restriction and placental insufficiency. Women with suspected or confirmed ZIKV infection should be monitored closely, with serial ultrasonography to evaluate for signs of placental insufficiency, given the risks of fetal death and intrauterine growth restriction. The establishment of a scientifically credible link between ZIKV and abnormal congenital findings is of utmost importance for the effective and successful management of this epidemic in Brazil and worldwide. This study was not supported by any research funds. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. This article was published on March 4, 2016, at NEJM.org. We thank the women who enrolled in this study, Mr. Marcelo dos Santos for assistance with the graphics of one of our figures, Dr. Yvonne Bryson for her ongoing support of our study, and Drs. Celina Boga and Eliane Chaves Vianna of the Centro de Saúde Escola Germano Sinval Faria–ENSP/FIOCRUZ for their continued support of our pregnancy cohort study. SOURCE INFORMATIONFrom Fundação Oswaldo Cruz, Rio de Janeiro (P.B., J.P.P.J., L.D., M.W., R.M.R.N., P.C.S., A.M.S., L.M.A.C., D.C.C., G.A.C., E.S.N., M.E.M., A.E.R.B., P.R.N.C., A.M.B.F.); Biomedical Research Institute of Southern California, Oceanside (C.R.G.); and David Geffen UCLA School of Medicine, Los Angeles (C.J., S.G.V., J.D.C., K.N.-S.). Address reprint requests to Dr. Nielsen-Saines at the Division of Pediatric Infectious Diseases, David Geffen School of Medicine at UCLA, MDCC 22-442, 10833 LeConte Ave., Los Angeles, CA 90095, or at [email protected].