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First 2016 Zika Sequence From United States Resident


niman

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Although confirmation of over 300 US Zika cases in 2015/2016 have been reported, including 278 on the CDC update page of confirmations in the US, no sequences have been released from US residents collected in 2015/2016.

Today a full sequence was accessible at Genbank.  The name of the sequence, FB-GWUH/2016 suggests it was collected on February 2, 2016 from a fetal brain at George Washington University Hospital, which is reflected in the "USA" origin from "fetal brain", as cited on the characterization page.

Moreover, the characterization sheet indicates that the patient was thought to have been infected in Guatemala, which is fully supported by the relatedness to the two Zika sequences at Genbank from Guatemala.

This data matches "Patient B" described in the CDC MMWR on pregnant Zika confirmed US residents, as well as a media report describing a Washington DC resident infected in Central America, who elected to terminate her pregnancy after Zika was confirmed in amniotic fluid and sonograms and MRI confirmed severe microcephaly in the fetus.

Although the CDC MMWR described the radiological confirmation of microcephaly and the patient was Zika confirmed by PCR,this case has not been cited in the WHO SitRep on confirmed microcephaly cases (the only US case is the full term infant in Hawaii).

Edited by niman
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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  JOURNAL   Unpublished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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Sequences producing significant alignments:

Select:AllNone Selected:0

Sequences producing significant alignments:
Select for downloading or viewing reportsDescriptionMax scoreTotal scoreQuery coverE valueIdentAccession
1842018420100%0.099%KU501217.1
1841718417100%0.099%KU501216.1
1837518375100%0.099%KU509998.1
1837218372100%0.099%KJ776791.1
1836318363100%0.099%KU707826.1
1836318363100%0.099%KU365779.1
1836318363100%0.099%KU321639.1
1835718357100%0.099%KU926309.1
1835418354100%0.099%KU729218.1
1834818348100%0.099%KU365780.1
1834518345100%0.099%KU365777.1
1833618336100%0.099%KU647676.1
1833018330100%0.099%KU365778.1
1833018330100%0.099%KU312312.1
1832718327100%0.099%KU729217.2
183271832799%0.099%KU497555.1
1832718327100%0.099%KU527068.1
1832118321100%0.099%KU820897.1
1832118321100%0.099%KU501215.1
1831818318100%0.099%KU922960.1
1831218312100%0.099%KU926310.1
1831218312100%0.099%KU922923.1
1830318303100%0.099%KU820898.1
1830318303100%0.099%KU853013.1
1830318303100%0.099%KU853012.1
1829418294100%0.099%KU740184.2
1829418294100%0.099%KU761564.1
1826718267100%0.099%KU820899.2
1815918159100%0.099%KU866423.1
1813718137100%0.099%KU744693.1
1802918029100%0.099%KU681081.3
177301773099%0.098%JN860885.1
176761767698%0.099%KF993678.1
1756717567100%0.098%EU545988.1
1742917429100%0.098%KU681082.3
163971639799%0.095%HQ234499.1
1328613286100%0.089%KU720415.1
132811328199%0.089%HQ234498.1
1327513275100%0.089%KF383115.1
1327013270100%0.089%KF268949.1
1327013270100%0.089%KF268948.1
1326313263100%0.089%LC002520.1
1326313263100%0.089%KF268950.1
1325913259100%0.089%KF383119.1
1324313243100%0.089%DQ859059.1
1323013230100%0.089%KF383116.1
132141321499%0.089%HQ234501.1
1320513205100%0.089%AY632535.2
1316013160100%0.088%KF383117.1
131441314499%0.088%HQ234500.1
1294513013100%0.088%KF383118.1
128551285597%0.089%KF383121.1
108771087797%0.084%KF383120.1
4967496727%0.099%KU312314.1
4940494027%0.099%KU312313.1
4655465525%0.099%KU646828.1
4646464625%0.099%KU646827.1
3440344018%0.099%KU312315.1
3214321417%0.099%KU740199.1
2879420695%0.071%DQ859064.1
2695269514%0.099%KJ634273.1
2042204211%0.099%KU686218.1
2021202111%0.099%KU179098.1
175217529%0.099%KM078936.1
174817489%0.099%KM078961.1
174617469%0.099%KM078930.1
174517459%0.099%KM078971.1
174517459%0.099%KM078970.1
174517459%0.099%KM078933.1
174317439%0.099%KM078929.1
160216028%0.099%KJ873160.1
142014207%0.099%KJ873161.1
138813887%0.099%KM851039.1
135213527%0.098%KM851038.1
134613467%0.099%KU556802.1
1306130610%0.088%AF013415.1
124012406%0.099%KU232300.1
124012406%0.099%KT200609.1
123112316%0.099%KU232290.1
122912296%0.099%KU232297.1
122012206%0.099%KU232294.1
121812186%0.099%KU232292.1
121412146%0.099%KU232298.1
121112116%0.099%KU232296.1
121112116%0.099%KU232293.1
120512056%0.099%KU232295.1
119511956%0.099%KU232288.1
119111916%0.099%KU232289.1
118711876%0.099%KU232299.1
118611866%0.099%KU232291.1
113011306%0.098%KU758878.1
106810688%0.088%KF270886.1
101810185%0.0100%KU867812.1
101110118%0.086%AF372422.1
9919917%0.088%KF270887.1
9759757%0.089%KF383022.1
975197764%0.070%EF158064.1
9719717%0.089%KF383026.1
9719717%0.088%EU303241.1
9629627%0.088%KF383032.1
9579577%0.088%KF383037.1
9579577%0.088%KF383034.1
9579577%0.088%KF383029.1
9539537%0.088%KF383033.1
9519517%0.088%KF383036.1
939178958%0.069%JX041632.1
9359357%0.088%KF383028.1
9339337%0.088%KF383039.1
931184654%0.069%GQ851605.1
9309307%0.087%KF383031.1
9249247%0.087%KF383038.1
9159157%0.087%KF383046.1
908190265%0.069%KT823415.1
908192365%0.069%FJ753286.2
9029027%0.087%KF383045.1
8978976%0.088%KF383103.1
8978976%0.088%KF383086.1
8978977%0.087%KF383043.1
8978977%0.086%KF383035.1
8938937%0.086%KF383041.1
8888887%0.086%KF383042.1
8658656%0.087%KF383104.1
8658656%0.087%KF383085.1
8638637%0.085%KF383040.1
8618616%0.087%KF383106.1
8568566%0.087%KF383114.1
8568566%0.087%KF383107.1
8568566%0.087%KF383088.1
8528526%0.087%KF383087.1
8388386%0.086%KF383089.1
8348346%0.086%KF383101.1
8348346%0.086%KF383097.1
8298296%0.086%KF383099.1
8298294%0.099%AB908162.1
8258256%0.086%KF383098.1
8148144%0.099%KU872850.1
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Sequences producing significant alignments:

Select:AllNone Selected:0

Sequences producing significant alignments:
Select for downloading or viewing reportsDescriptionMax scoreTotal scoreQuery coverE valueIdentAccession
1852518525100%0.0100%KU870645.1
1842018420100%0.099%KU501217.1
1841718417100%0.099%KU501216.1
1837518375100%0.099%KU509998.1
1837218372100%0.099%KJ776791.1
1836318363100%0.099%KU707826.1
1836318363100%0.099%KU365779.1
1836318363100%0.099%KU321639.1
1835718357100%0.099%KU926309.1
1835418354100%0.099%KU729218.1
1834818348100%0.099%KU365780.1
1834518345100%0.099%KU365777.1
1833618336100%0.099%KU647676.1
1833018330100%0.099%KU365778.1
1833018330100%0.099%KU312312.1
1832718327100%0.099%KU729217.2
183271832799%0.099%KU497555.1
1832718327100%0.099%KU527068.1
1832118321100%0.099%KU820897.1
1832118321100%0.099%KU501215.1
1831818318100%0.099%KU922960.1
1831218312100%0.099%KU926310.1
1831218312100%0.099%KU922923.1
1830318303100%0.099%KU820898.1
1830318303100%0.099%KU853013.1
1830318303100%0.099%KU853012.1
1830018300100%0.099%KU955590.1
1829418294100%0.099%KU740184.2
1829418294100%0.099%KU761564.1
1826718267100%0.099%KU955589.1
1826718267100%0.099%KU820899.2
1815918159100%0.099%KU866423.1
1813718137100%0.099%KU744693.1
1802918029100%0.099%KU681081.3
1773217732100%0.098%KU955593.1
177301773099%0.098%JN860885.1
176761767698%0.099%KF993678.1
1756717567100%0.098%EU545988.1
1742917429100%0.098%KU681082.3
163971639799%0.095%HQ234499.1
1328613286100%0.089%KU720415.1
132811328199%0.089%HQ234498.1
1327513275100%0.089%KF383115.1
1327213272100%0.089%KU955595.1
1327013270100%0.089%KF268949.1
1327013270100%0.089%KF268948.1
1326313263100%0.089%KU955592.1
1326313263100%0.089%LC002520.1
1326313263100%0.089%KF268950.1
1325913259100%0.089%KF383119.1
1324713247100%0.089%KU955594.1
1324513245100%0.089%KU955591.1
1324313243100%0.089%DQ859059.1
1323013230100%0.089%KF383116.1
132141321499%0.089%HQ234501.1
1320513205100%0.089%AY632535.2
1316013160100%0.088%KF383117.1
131441314499%0.088%HQ234500.1
1294513013100%0.088%KF383118.1
128551285597%0.089%KF383121.1
108771087797%0.084%KF383120.1
4967496727%0.099%KU312314.1
4940494027%0.099%KU312313.1
4655465525%0.099%KU646828.1
4646464625%0.099%KU646827.1
3440344018%0.099%KU312315.1
3214321417%0.099%KU740199.1
2879420695%0.071%DQ859064.1
2695269514%0.099%KJ634273.1
2042204211%0.099%KU686218.1
2021202111%0.099%KU179098.1
175217529%0.099%KM078936.1
174817489%0.099%KM078961.1
174617469%0.099%KM078930.1
174517459%0.099%KM078971.1
174517459%0.099%KM078970.1
174517459%0.099%KM078933.1
174317439%0.099%KM078929.1
160216028%0.099%KJ873160.1
142014207%0.099%KJ873161.1
138813887%0.099%KM851039.1
135213527%0.098%KM851038.1
134613467%0.099%KU556802.1
1306130610%0.088%AF013415.1
124012406%0.099%KU232300.1
124012406%0.099%KT200609.1
123112316%0.099%KU232290.1
122912296%0.099%KU232297.1
122012206%0.099%KU232294.1
121812186%0.099%KU232292.1
121412146%0.099%KU232298.1
121112116%0.099%KU232296.1
121112116%0.099%KU232293.1
120512056%0.099%KU232295.1
119511956%0.099%KU232288.1
119111916%0.099%KU232289.1
118711876%0.099%KU232299.1
118611866%0.099%KU232291.1
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Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities

Rita W. Driggers, M.D., Cheng-Ying Ho, M.D., Ph.D., Essi M. Korhonen, M.Sc., Suvi Kuivanen, M.Sc., Anne J. Jääskeläinen, Ph.D., Teemu Smura, Ph.D., Avi Rosenberg, M.D., Ph.D., D. Ashley Hill, M.D., Roberta L. DeBiasi, M.D., Gilbert Vezina, M.D., Julia Timofeev, M.D., Fausto J. Rodriguez, M.D., Lev Levanov, Ph.D., Jennifer Razak, M.G.C., C.G.C, Preetha Iyengar, M.D., Andrew Hennenfent, D.V.M., M.P.H., Richard Kennedy, M.D., Robert Lanciotti, Ph.D., Adre du Plessis, M.B., Ch.B., M.P.H., and Olli Vapalahti, M.D., Ph.D.

March 30, 2016DOI: 10.1056/NEJMoa1601824

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

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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.

Fetal MRI at 20 weeks of gestation showed diffuse atrophy of the cerebral mantle, which was most severe in the frontal and parietal lobes, with the anterior temporal lobes least affected (Figure 3FIGURE 3nejmoa1601824_f3.gifMagnetic Resonance Imaging of the Fetal Brain at 19 Weeks of Gestation.). The normal lamination pattern of the cerebral mantle was absent, and the subplate zone was largely undetectable. The corpus callosum was significantly shorter than expected for gestational age, with an anterior–posterior length of 14 mm (expected range, 18 to 22).18,19 The cavum septum pellucidum was very small. The lateral ventricles were mildly enlarged, as was the third ventricle, with a transverse diameter measuring 2.5 mm (average measurement at gestational age, 1.75 mm [range, 1.1 to 2.3]).18 The fourth ventricle was normal. The volume of the choroid plexus was unusually prominent, without evidence of hemorrhage. No focal destructive lesions were identified within the cerebral cortex or white matter. The cerebellum was normal in appearance and size. Given the grave prognosis, the patient elected to terminate the pregnancy at 21 weeks of gestation.

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