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Zika Linked Fetal Brain Disruption Sequence Washington DC ex-Guatemala


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Patient B. In January 2016, a pregnant woman in her 30s underwent laboratory testing for Zika virus infection. She reported a history of travel to a Zika-affected area at approximately 11–12 weeks’ gestation. One day after returning from travel, she developed fever, eye pain, and myalgia. The next day, she developed a rash. Serologic testing confirmed recent Zika virus infection. At approximately 20 weeks’ gestation, she underwent a fetal ultrasound that suggested absence of the corpus callosum, ventriculomegaly, and brain atrophy; subsequent fetal magnetic resonance imaging demonstrated severe brain atrophy. Amniocentesis was performed, and Zika virus RNA was detected by RT-PCR testing. After discussion with her health care providers, the patient elected to terminate her pregnancy.

http://www.cdc.gov/mmwr/volumes/65/wr/mm6508e1.htm?s_cid=mm6508e1_w

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The pregnant woman was in her 30s and, like a growing number of patients at Richard Newman's practice in downtown Washington, worried about a threat the obstetrician himself had learned about only recently: Zika.

In December, during her first trimester, she'd taken a vacation to Central America. Weeks later, U.S. officials began warning pregnant women about traveling to regions where the virus was spreading rapidly. She'd gotten a mosquito bite, followed by a rash, fever and joint pain -- all potential symptoms of infection.

Newman recommended she see a specialist at Sibley Memorial Hospital and encouraged her to have her blood tested by the Centers for Disease Control and Prevention. He'd already done the same for more than a dozen anxious patients in 2016, and each time the results were negative

This time, the test came back positive.

 

The outcome was different for the expectant mother at Newman's practice.

Everything looked fine on the sonogram he'd ordered when she was 16 weeks along. But the image a month later showed distinct abnormalities with "very little brain development," Newman said. A fetal MRI confirmed severe brain atrophy, and analysis of the woman's amniotic fluid detected the presence of Zika.

Newman told his patient that the results suggested her child, if carried to term, might not survive long and almost certainly would have "no chance for a normal quality of life."

Last month, after the final tests results came in, the woman called and told him she planned to terminate the pregnancy.

"I just listened and sympathized," he said. "I can only imagine how hard this was for her. ... It was one of the saddest moments of my medical career."

http://www.chicagotribune.com/news/nationworld/ct-zika-virus-pregnant-women-20160307-story.html

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LOCUS       KU870645               10798 bp    RNA     linear   VRL 22-MAR-2016
DEFINITION  Zika virus isolate FB-GWUH-2016, complete genome.
ACCESSION   KU870645
VERSION     KU870645.1  GI:1006593136
KEYWORDS    .
SOURCE      Zika virus
  ORGANISM  Zika virus
            Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA
            stage; Flaviviridae; Flavivirus.
REFERENCE   1  (bases 1 to 10798)
  AUTHORS   Driggers,R.W., Ho,C.-Y., Korhonen,E.M., Kuivanen,S.,
            Jaaskelainen,A.J., Smura,T., Rosenberg,A., Hill,A., DeBiasi,R.,
            Vezina,G., Timofeev,J., Rodriguez,F.J., Levanov,L., Razak,J.,
            Iyengar,P., Hennenfent,A., Kennedy,R., Lanciotti,R., du Plessis,A.
            and Vapalahti,O.
  TITLE     Zika virus infection with prolonged maternal viremia and fetal
            brain abnormalities
  JOURNAL   Unpublished
REFERENCE   2  (bases 1 to 10798)
  AUTHORS   Smura,T., Korhonen,E., Kuivanen,S. and Vapalahti,O.
  TITLE     Direct Submission
  JOURNAL   Submitted (05-MAR-2016) Department of Virology, University of
            Helsinki, Haartmaninkatu 3, Helsinki 00280, Finland
FEATURES             Location/Qualifiers
     source          1..10798
                     /organism="Zika virus"
                     /mol_type="genomic RNA"
                     /isolate="FB-GWUH-2016"
                     /isolation_source="fetal brain"
                     /host="Homo sapiens"
                     /db_xref="taxon:64320"
                     /country="USA"
                     /collection_date="02-Feb-2016"
                     /note="putative country of infection: Guatemala;
                     passage details: SK-N-SH"

http://www.ncbi.nlm.nih.gov/nuccore/KU870645

 

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CASE REPORT

A 33-year-old Finnish woman who was in the 11th week of gestation was on holiday in Mexico, Guatemala, and Belize with her husband in late November 2015. (Details are provided in Section 1.0 of the Supplementary Appendix, available with the full text of this article at NEJM.org.) During their travels, she and her husband recalled being bitten by mosquitoes, particularly in Guatemala. One day after her arrival at her current residence in Washington, D.C., she became ill with ocular pain, myalgia, and mild fever (maximum, 37.5°C), which lasted for 5 days. On the second day of fever, a rash developed (Figure 1FIGURE 1nejmoa1601824_f1.gifTimeline of Symptoms and Radiographic and Laboratory Studies., and Fig. S5 in the Supplementary Appendix). Her husband was concomitantly reporting similar symptoms. Serologic analysis that was performed 4 weeks after the onset of illness while she was on a trip to her native Finland was positive for IgG antibodies and negative for IgM antibodies against dengue virus. Subsequent serologic analysis was positive for both IgG and IgM antibodies against ZIKV, findings that were compatible with acute or recent ZIKV infection. Serologic analysis for the presence of chikungunya virus was negative. The patient had been vaccinated against tick-borne encephalitis and yellow fever more than 10 years earlier.

Fetal ultrasonography that was performed at 13, 16, and 17 weeks of gestation (1, 4, and 5 weeks after the resolution of symptoms) showed no evidence of microcephaly or intracranial calcifications. However, there was a decrease in the fetal head circumference from the 47th percentile at 16 weeks to the 24th percentile at 20 weeks.

At 16 weeks of gestation, the presence of flavivirus in serum was detected on nested reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay, and sequencing showed identity to Central American epidemic strains of ZIKV. The finding was confirmed with a specific ZIKV quantitative RT-PCR assay (Table S2 in the Supplementary Appendix). The Division of Vector-Borne Diseases Arbovirus Diagnostic Laboratory at the CDC reported serologic evidence of infection at 17 weeks of gestation, with serum positivity for ZIKV IgM and a titer of more than 1:2560 on a plaque-reduction neutralization test. On the basis of these results, the patient sought more thorough assessment of the fetus.

Fetal ultrasonography at 19 weeks of gestation showed abnormal intracranial anatomy (Figure 2FIGURE 2nejmoa1601824_f2.gifFetal Ultrasonography at 19 Weeks of Gestation., and Fig. S1 in the Supplementary Appendix). The cerebral mantle appeared to be thin with increased extra-axial spaces. Both frontal horns were enlarged with heterogeneous, predominantly echogenic material present in the frontal horn and body of the left lateral ventricle, a finding that raised concern about intraventricular hemorrhage. Dilation and upward displacement of the third ventricle, dilation of the frontal horns of the lateral ventricles, concave medial borders of the lateral ventricles, and the absence of the cavum septum pellucidum suggested agenesis of the corpus callosum. No parenchymal calcifications were seen. The head circumference measured in the 24th percentile for gestational age. The remainder of the fetal anatomy was normal.

http://www.nejm.org/doi/full/10.1056/NEJMoa1601824#t=article

 

Edited by niman
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