Download pdf - Zika Virus Associated With Microcephaly

8/19/2019 Zika Virus Associated With Microcephaly

1/23

CONTENT

Zika virus

From Wikipedia, the free encyclopediaThis article is about the virus. For the disease, see Zika fever . For the 2015–16 outbreak, see Zikavirus outbreak (2015–present .

Zika virus

Electron micrograph of Zikavirus. Virus particles are

40 nm in diameter, with anouter envelope and a denseinner core (source: C C!.

Virus classifcation

https://en.wikipedia.org/wiki/Zika_feverhttps://en.wikipedia.org/wiki/Zika_virus_outbreak_(2015%E2%80%93present)https://en.wikipedia.org/wiki/Zika_virus_outbreak_(2015%E2%80%93present)https://en.wikipedia.org/wiki/Zika_virus_outbreak_(2015%E2%80%93present)https://en.wikipedia.org/wiki/Electron_micrographhttps://en.wikipedia.org/wiki/Nanometrehttps://en.wikipedia.org/wiki/Virus_classificationhttps://en.wikipedia.org/wiki/Zika_virus_outbreak_(2015%E2%80%93present)https://en.wikipedia.org/wiki/Zika_virus_outbreak_(2015%E2%80%93present)https://en.wikipedia.org/wiki/Electron_micrographhttps://en.wikipedia.org/wiki/Nanometrehttps://en.wikipedia.org/wiki/Virus_classificationhttps://en.wikipedia.org/wiki/Zika_fever


2/23

"roup: "roup #V (($!ss%&' !

amil): Flaviviridae

"enus: Flavivirus

*pecies: Zika virus

Zika virus / zi kə,+ z kə/+ - [1][2][3][4] (ZIKV) i a mem!er of the "ir# family Flaviviridae andthe $en# Flavivirus , tran mitted !y daytime%acti"e !edes mo itoe , #ch a !. ae"#pti and !.albopictus ' t name come from the ika Fore t of *$anda , +here the "ir# +a fir t i olated in

1 4-'[.]

ika "ir# i related to den$#e , yello+ fe"er , apane e encephaliti , and We t 0ile "ir# e '[ ]

he infection, kno+n a ika fe"er , often ca# e no or only mild ymptom , imilar to a mild form

of den$#e fe"er ' [ ] t i treated !y re t' [-] ince the 1 . , it ha !een kno+n to occ#r +ithin a narro+eatorial !elt from 5frica to 5 ia' n 2 14, the "ir# pread ea t+ard acro the 6acific 7ceanto French 6olyne ia , then to 8a ter land and in 2 1. to 9e:ico, ;entral 5merica, the ;ari!!ean,

and o#th 5merica, +here the ika o#t!reak ha reached pandemic le"el ' [


3/23

• 1 Cirolo$y

• 2 ran mi ion

o 2'1 Cector

o 2'2 e:#al

o 2'3 A#rin$ pre$nancy

o 2'4 7ther, #npro"en

• 3 ika fe"er • 4 Caccine de"elopment

• . Di tory

o .'1 Cir# i olation in monkey and mo itoe ,1 4-

o .'2 Fir t e"idence of h#man infection, 1 .2

o .'3 pread in eatorial 5frica and to 5 ia, 1 .1>1 2 14o .' 5merica , 2 1.>pre ent

• ee al o

https://en.wikipedia.org/wiki/Zika_virus#Virologyhttps://en.wikipedia.org/wiki/Zika_virus#Transmissionhttps://en.wikipedia.org/wiki/Zika_virus#Vectorhttps://en.wikipedia.org/wiki/Zika_virus#Sexualhttps://en.wikipedia.org/wiki/Zika_virus#During_pregnancyhttps://en.wikipedia.org/wiki/Zika_virus#Other.2C_unprovenhttps://en.wikipedia.org/wiki/Zika_virus#Zika_feverhttps://en.wikipedia.org/wiki/Zika_virus#Vaccine_developmenthttps://en.wikipedia.org/wiki/Zika_virus#Historyhttps://en.wikipedia.org/wiki/Zika_virus#Virus_isolation_in_monkeys_and_mosquitoes.2C_1947https://en.wikipedia.org/wiki/Zika_virus#Virus_isolation_in_monkeys_and_mosquitoes.2C_1947https://en.wikipedia.org/wiki/Zika_virus#First_evidence_of_human_infection.2C_1952https://en.wikipedia.org/wiki/Zika_virus#Spread_in_equatorial_Africa_and_to_Asia.2C_1951.E2.80.931981https://en.wikipedia.org/wiki/Zika_virus#Spread_in_equatorial_Africa_and_to_Asia.2C_1951.E2.80.931981https://en.wikipedia.org/wiki/Zika_virus#Micronesia.2C_2007https://en.wikipedia.org/wiki/Zika_virus#Oceania.2C_2013.E2.80.932014https://en.wikipedia.org/wiki/Zika_virus#Americas.2C_2015.E2.80.93presenthttps://en.wikipedia.org/wiki/Zika_virus#See_alsohttps://en.wikipedia.org/wiki/Zika_virus#Virologyhttps://en.wikipedia.org/wiki/Zika_virus#Transmissionhttps://en.wikipedia.org/wiki/Zika_virus#Vectorhttps://en.wikipedia.org/wiki/Zika_virus#Sexualhttps://en.wikipedia.org/wiki/Zika_virus#During_pregnancyhttps://en.wikipedia.org/wiki/Zika_virus#Other.2C_unprovenhttps://en.wikipedia.org/wiki/Zika_virus#Zika_feverhttps://en.wikipedia.org/wiki/Zika_virus#Vaccine_developmenthttps://en.wikipedia.org/wiki/Zika_virus#Historyhttps://en.wikipedia.org/wiki/Zika_virus#Virus_isolation_in_monkeys_and_mosquitoes.2C_1947https://en.wikipedia.org/wiki/Zika_virus#Virus_isolation_in_monkeys_and_mosquitoes.2C_1947https://en.wikipedia.org/wiki/Zika_virus#First_evidence_of_human_infection.2C_1952https://en.wikipedia.org/wiki/Zika_virus#Spread_in_equatorial_Africa_and_to_Asia.2C_1951.E2.80.931981https://en.wikipedia.org/wiki/Zika_virus#Spread_in_equatorial_Africa_and_to_Asia.2C_1951.E2.80.931981https://en.wikipedia.org/wiki/Zika_virus#Micronesia.2C_2007https://en.wikipedia.org/wiki/Zika_virus#Oceania.2C_2013.E2.80.932014https://en.wikipedia.org/wiki/Zika_virus#Americas.2C_2015.E2.80.93presenthttps://en.wikipedia.org/wiki/Zika_virus#See_also


4/23

• - Beference

• < 8:ternal link

Virology

5 "ideo e:planation of ika "ir# and ika fe"er

he ika "ir# !elon$ to Fla"i"iridae and the $en# Flavivirus , and i th# related tothe den$#e , yello+ fe"er , apane e encephaliti , and We t 0ile "ir# e ' Eike other fla"i"ir# e , ika"ir# i en"eloped and ico ahedral and ha a non e$mented, in$le% tranded, po iti"e%

en e B05 $enome' t i mo t clo ely related to the pond+eni "ir# and i one of the t+o "ir# e

in the pond+eni "ir# clade ' [2 ][21]

5 po iti"e% en e B05 $enome can !e directly tran lated into "iral protein ' n other fla"i"ir# e ,#ch a the imilarly ized We t 0ile "ir# , the B05 $enome $ene encode e"en non tr#ct#ral

protein and three tr#ct#ral protein ' he tr#ct#ral protein encap #late the "ir# ' he replicatedB05 trand i held +ithin a n#cleocap id formed from 12%kAa protein !lock the cap id i contained+ithin a ho t%deri"ed mem!rane modified +ith t+o "iral $lycoprotein ' Beplication of the "iral

$enome +o#ld fir t reire creation of an anti% en e n#cleotide trand' [citation needed ]

here are t+o linea$e of the ika "ir# G the 5frican linea$e, and the 5 ian linea$e' [22] 6hylo$enetict#die indicate that the "ir# preadin$ in the 5merica i mo t clo ely related to the 5 ian train,

+hich circ#lated in French 6olyne ia d#rin$ the 2 13 o#t!reak' [22][23] he complete $enome

eence of the ika "ir# ha !een p#!li hed' [24]

Transmission

he "erte!rate ho t of the "ir# +ere primarily monkey in a o%called enzootic mo ito%monkey%mo ito cycle, +ith only occa ional tran mi ion to h#man ' ?efore the c#rrent pandemic !e$an in2 -, ika "ir# Hrarely ca# ed reco$nized I pillo"erI infection in h#man , e"en in hi$hly enzooticarea H' nfreently, other ar!o"ir# e ha"e !ecome e ta!li hed a a h#man di ea e tho#$h, and

pread in a mo ito>h#man>mo ito cycle, like the yello+ fe"er "ir# and the den$#e fe"er "ir#

(!oth fla"ir# e ), and the chik#n$#nya "ir# (a to$a"ir# )' [13]

https://en.wikipedia.org/wiki/Zika_virus#Referenceshttps://en.wikipedia.org/wiki/Zika_virus#External_linkshttps://en.wikipedia.org/wiki/Flaviviridaehttps://en.wikipedia.org/wiki/Flaviviridaehttps://en.wikipedia.org/wiki/Flavivirushttps://en.wikipedia.org/wiki/Dengue_virushttps://en.wikipedia.org/wiki/Dengue_virushttps://en.wikipedia.org/wiki/Yellow_fever#Causehttps://en.wikipedia.org/wiki/Yellow_fever#Causehttps://en.wikipedia.org/wiki/Japanese_encephalitishttps://en.wikipedia.org/wiki/Japanese_encephalitishttps://en.wikipedia.org/wiki/West_Nile_virushttps://en.wikipedia.org/wiki/Viral_envelopehttps://en.wikipedia.org/wiki/Viral_envelopehttps://en.wikipedia.org/wiki/Icosahedralhttps://en.wikipedia.org/wiki/Icosahedralhttps://en.wikipedia.org/wiki/Icosahedralhttps://en.wikipedia.org/wiki/Sense_(molecular_biology)https://en.wikipedia.org/wiki/Sense_(molecular_biology)https://en.wikipedia.org/wiki/RNAhttps://en.wikipedia.org/wiki/Spondweni_virushttps://en.wikipedia.org/wiki/Cladehttps://en.wikipedia.org/wiki/Cladehttps://en.wikipedia.org/wiki/Zika_virus#cite_note-Fields-20https://en.wikipedia.org/wiki/Zika_virus#cite_note-Fields-20https://en.wikipedia.org/wiki/Zika_virus#cite_note-21https://en.wikipedia.org/wiki/Positive-sense_RNAhttps://en.wikipedia.org/wiki/Nucleocapsidhttps://en.wikipedia.org/wiki/Nucleocapsidhttps://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttps://en.wikipedia.org/wiki/Zika_virus#cite_note-Enfissi16-22https://en.wikipedia.org/wiki/Zika_virus#cite_note-Enfissi16-22https://en.wikipedia.org/wiki/Zika_virus#cite_note-23https://en.wikipedia.org/wiki/Zika_virus#cite_note-24https://en.wikipedia.org/wiki/Monkeyhttps://en.wikipedia.org/wiki/Enzootichttps://en.wikipedia.org/wiki/Enzootichttps://en.wikipedia.org/wiki/Pandemichttps://en.wikipedia.org/wiki/Pandemichttps://en.wikipedia.org/wiki/Arbovirushttps://en.wikipedia.org/wiki/Arbovirushttps://en.wikipedia.org/wiki/Chikungunyahttps://en.wikipedia.org/wiki/Chikungunyahttps://en.wikipedia.org/wiki/Zika_virus#cite_note-Fauci2016nejm-13https://en.wikipedia.org/wiki/Zika_virus#Referenceshttps://en.wikipedia.org/wiki/Zika_virus#External_linkshttps://en.wikipedia.org/wiki/Flaviviridaehttps://en.wikipedia.org/wiki/Flavivirushttps://en.wikipedia.org/wiki/Dengue_virushttps://en.wikipedia.org/wiki/Yellow_fever#Causehttps://en.wikipedia.org/wiki/Japanese_encephalitishttps://en.wikipedia.org/wiki/West_Nile_virushttps://en.wikipedia.org/wiki/Viral_envelopehttps://en.wikipedia.org/wiki/Icosahedralhttps://en.wikipedia.org/wiki/Sense_(molecular_biology)https://en.wikipedia.org/wiki/Sense_(molecular_biology)https://en.wikipedia.org/wiki/RNAhttps://en.wikipedia.org/wiki/Spondweni_virushttps://en.wikipedia.org/wiki/Cladehttps://en.wikipedia.org/wiki/Zika_virus#cite_note-Fields-20https://en.wikipedia.org/wiki/Zika_virus#cite_note-21https://en.wikipedia.org/wiki/Positive-sense_RNAhttps://en.wikipedia.org/wiki/Nucleocapsidhttps://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttps://en.wikipedia.org/wiki/Zika_virus#cite_note-Enfissi16-22https://en.wikipedia.org/wiki/Zika_virus#cite_note-Enfissi16-22https://en.wikipedia.org/wiki/Zika_virus#cite_note-23https://en.wikipedia.org/wiki/Zika_virus#cite_note-24https://en.wikipedia.org/wiki/Monkeyhttps://en.wikipedia.org/wiki/Enzootichttps://en.wikipedia.org/wiki/Pandemichttps://en.wikipedia.org/wiki/Arbovirushttps://en.wikipedia.org/wiki/Chikungunyahttps://en.wikipedia.org/wiki/Zika_virus#cite_note-Fauci2016nejm-13


5/23

Cector

=lo!al !edes ae"#pti predicted di tri!#tion' he map depictthe pro!a!ility of occ#rrence (!l#eJnone, redJhi$he tocc#rrence)'

he ika "ir# i tran mitted !y daytime%acti"e mo itoe a it "ector ' t i primarily tran mitted !y

the female !edes ae"#pti in order to lay e$$ , [2.] G2 !#t ha !een i olated from a n#m!erof ar!oreal mo ito pecie in the !edes $en# , #ch a !. africanus , !. apicoar"enteus , !.furcifer , !. hensilli , !. luteocephalus and !. vittatus +ith an e:trin ic inc#!ation period in mo itoe

of a!o#t 1 day ' [2 ]

he tr#e e:tent of the "ector i till #nkno+n' he ika "ir# ha !een detected in many morepecie of !edes , alon$ +ith !nopheles coustani, $ansonia unifor%is , and &ule' perfuscus ,

altho#$h thi alone doe not incriminate them a a "ector' [2-]

ran mi ion !y !. albopictus , the ti$er mo ito, +a reported from a 2 - #r!an o#t!reak in=a!on +here it had ne+ly in"aded the co#ntry and !ecome the primary "ector for the concomitant

chik#n$#nya and den$#e "ir# o#t!reak ' [2


6/23

ince 2 1., ne+ report ha"e dra+n attention to the pread of ika in Eatin 5merica and the

;ari!!ean ' [33] he co#ntrie and territorie that ha"e !een identified !y the 6an 5merican Dealth7r$ani ation a ha"in$ e:perienced Hlocal ika "ir# tran mi ionH are ?ar!ado , ?oli"ia, ?razil,;olom!ia, the Aominican Bep#!lic, 8c#ador, 8l al"ador, French =#iana, =#adelo#pe, =#atemala,=#yana, Daiti, Dond#ra , 9artinie, 9e:ico, 6anama, 6ara$#ay, 6#erto Bico, aint 9artin,

#riname, and Cenez#ela' [34][3.]

e:#al

5 of Fe!r#ary 2 1 , three reported ca e indicate that ika "ir# co#ld po i!ly !e e:#allytran mitted ' n 2 14, ika "ir# capa!le of reprod#cin$ it elf +a fo#nd in the emen of a man at

lea t t+o +eek (and po i!ly #p to 1 +eek ) after he fell ill +ith ika fe"er' [3 ][3-] he econdreport i of a *nited tate !iolo$i t +ho had !een !itten many time +hile t#dyin$ mo itoe in

ene$al' i: day after ret#rnin$ home in 5#$# t 2


7/23

5ccordin$ to the WD7 on . Fe!r#ary 2 1 , a ca# al link !et+een the ika "ir# and microcephaly+a H tron$ly # pected !#t not yet cientifically pro"enH and H5ltho#$h the microcephaly ca e in?razil are patio%temporally a ociated +ith the ika o#t!reak, more ro!# t in"e ti$ation and

re earch i needed to !etter #nder tand thi potential link'H [44]

7n . Fe!r#ary 2 1 , the *nited tate ;A; #pdated it health care pro"ider $#ideline for pre$nant+omen and +omen of reprod#cti"e a$e' he ne+ recommendation incl#de offerin$ erolo$icte tin$ to pre$nant +omen +itho#t ika fe"er ymptom +ho ha"e ret#rned from area +ith on$oin$

ika "ir# tran mi ion in the la t 2>12 +eek and for pre$nant +omen +itho#t ika ymptomli"in$ in #ch area , they recommend te tin$ at the !e$innin$ of prenatal care and follo+%#p te tin$

in the fifth month of pre$nancy ' [4.]

7ther, #npro"en

5 of Fe!r#ary 2 1 there are no confirmed ca e of ika "ir# tran mi ion thro#$h !lood

tran f# ion ' [4 ] 5 potential ri k i #pected !a ed on a t#dy cond#cted !et+een 0o"em!er 2 13and Fe!r#ary 2 14 d#rin$ the ika o#t!reak in French 6olyne ia in +hich 2'


8/23

and pro$re ed to a mac#lopap#lar ra h, fe"er, and !ack pain' Within t+o day , the ra h tartedfadin$, and +ithin three day , the fe"er re ol"ed and only the ra h remained' h# far, ika fe"erha !een a relati"ely mild di ea e of limited cope, +ith only one in fi"e per on de"elopin$

ymptom , +ith no fatalitie , !#t it tr#e potential a a "iral a$ent of di ea e i #nkno+n' [2 ]

5 of 2 1 , no "accine or pre"entati"e dr#$ i a"aila!le' ymptom can !e treated +ith re t, fl#id ,and paracetamol (acetaminophen), +hile a pirin and other non teroidal anti%inflammatory

dr#$ ho#ld !e # ed only +hen den$#e ha !een r#led o#t to red#ce the ri k of !leedin$' [4


9/23

;o#ntrie that ha"e pa t or c#rrent e"idence of ika "ir#tran mi ion (a of an#ary 2 1 ) [. ]

pread of the ika "ir# [.-]hi file i a candidate for peedy deletion ' t may !e deleted after Wedne day, 1-

Fe!r#ary 2 1 '

Cir# i olation in monkey and mo itoe , 1 4-

he "ir# +a fir t i olated in 5pril 1 4- from a rhe # macae monkey that had !een placed in aca$e in the ika Fore t of *$anda , near Eake Cictoria , !y the cienti t of the Mello+ Fe"er

Be earch n tit#te ' [.


10/23

ika "ir# had !een kno+n to infect h#man from the re #lt of erolo$ical #r"ey in *$anda and0i$eria' 5 ero #r"ey of 2 14

his sectionre/uires e pansion .(February2016)

$ain article 201/–201 Zika virus outbreaks in ceania

https://en.wikipedia.org/wiki/Zika_virus#cite_note-Dick52-61https://en.wikipedia.org/wiki/Wikipedia:Please_clarifyhttps://en.wikipedia.org/wiki/Wikipedia:Please_clarifyhttps://en.wikipedia.org/wiki/Wikipedia:Please_clarifyhttps://en.wikipedia.org/wiki/Zika_virus#cite_note-Dick52-61https://en.wikipedia.org/wiki/Zika_virus#cite_note-62https://en.wikipedia.org/wiki/Zika_virus#cite_note-EID-26https://en.wikipedia.org/wiki/Zika_virus#cite_note-EID-26https://en.wikipedia.org/wiki/Zika_virus#cite_note-63https://en.wikipedia.org/wiki/2007_Yap_Islands_Zika_virus_outbreakhttps://en.wikipedia.org/wiki/2007_Yap_Islands_Zika_virus_outbreakhttps://en.wikipedia.org/wiki/Yaphttps://en.wikipedia.org/wiki/Ross_River_virushttps://en.wikipedia.org/wiki/Ross_River_virushttps://en.wikipedia.org/wiki/Zika_virus#cite_note-64https://en.wikipedia.org/wiki/Zika_virus#cite_note-65https://en.wikipedia.org/w/index.php?title=Zika_virus&action=edithttps://en.wikipedia.org/wiki/2013%E2%80%932014_Zika_virus_outbreaks_in_Oceaniahttps://en.wikipedia.org/wiki/2013%E2%80%932014_Zika_virus_outbreaks_in_Oceaniahttps://en.wikipedia.org/wiki/Zika_virus#cite_note-Dick52-61https://en.wikipedia.org/wiki/Wikipedia:Please_clarifyhttps://en.wikipedia.org/wiki/Zika_virus#cite_note-Dick52-61https://en.wikipedia.org/wiki/Zika_virus#cite_note-62https://en.wikipedia.org/wiki/Zika_virus#cite_note-EID-26https://en.wikipedia.org/wiki/Zika_virus#cite_note-63https://en.wikipedia.org/wiki/2007_Yap_Islands_Zika_virus_outbreakhttps://en.wikipedia.org/wiki/Yaphttps://en.wikipedia.org/wiki/Ross_River_virushttps://en.wikipedia.org/wiki/Zika_virus#cite_note-64https://en.wikipedia.org/wiki/Zika_virus#cite_note-65https://en.wikipedia.org/w/index.php?title=Zika_virus&action=edithttps://en.wikipedia.org/wiki/2013%E2%80%932014_Zika_virus_outbreaks_in_Oceania


11/23

?et+een 2 13 and 2 14, f#rther epidemic occ#rred in French 6olyne ia 6olyne ia, 8a ter land,

the ;ook land , and 0e+ ;aledonia ' [4]

5merica , 2 1.>pre ent

$ain article Zika virus outbreak (2015–present

ince 5pril 2 1., a lar$e, on$oin$ o#t!reak of ika "ir# that !e$an in ?razil ha pread to m#chof o#th and ;entral 5merica and the ;ari!!ean ' n an#ary 2 1 , the ;A; i #ed a le"el 2 tra"elalert for people tra"elin$ to re$ion and certain co#ntrie +here ika "ir# tran mi ion i on$oin$,[ ] and #$$e ted that +omen thinkin$ a!o#t !ecomin$ pre$nant ho#ld con #lt +ith their

phy ician !efore tra"elin$' [ -] =o"ernment or health a$encie of the *nited Nin$dom, [1 ] reland,[1-] 0e+ ealand, [


12/23

Jerne Mlakar! M"#"! Misa $or%a! &h"#"! 'ata(a Tul! M"#"! &h"#"! Mara &opo%i)! M"#"! &h"#"! Mate a &ol (ak*&ri atel ! &h"

Mra+! M"Sc"! Marko $olenc! M"Sc"! $atarina Res,an Rus! M"Sc"! Tina Vesna%er Vipotnik! M"#"! Vesna -a. an Vodu(ek! M"#"! Alenk

Vi+ ak! &h"#"! Jo/e &i/e,! M"#"! &h"#"! Mirosla% &etro%ec! M"#"! &h"#"! and Tat ana A%(i0 1upanc! &h"#"

-e.ruary 23! 4325#6I7 23"23859'EJMoa2533582hareG

AbstractArticleReferencesCiting Articles (1)

NC, an emer$in$ mo ito%!orne fla"i"ir# , +ainitially i olated from a rhe # monkey in the ikafore t in *$anda in 1 4-' 1 t i tran mitted !y "ario#

pecie of aede mo itoe ' 5fter the fir t h#manNC infection, poradic ca e +ere reported in

o#thea t 5 ia and #!% aharan 5frica' 2 NC +are pon i!le for the o#t!reak in Map land of9icrone ia in 2 - and for maLor epidemic in French6olyne ia, 0e+ ;aledonia, the ;ook land , and8a ter land in 2 13 and 2 14' 3,4 n 2 1., there +aa dramatic increa e in report of NC infection in the

5merica ' ?razil i the mo t affected co#ntry, +ithpreliminary e timate of 44 , to 1'3 million ca eof a#tochthono# NC infection reported thro#$hAecem!er 2 1.' .

he cla ic clinical pict#re of NC infectionre em!le that of den$#e fe"er and chik#n$#nya and

i manife ted !y fe"er, headache, arthral$ia, myal$ia,and mac#lopap#lar ra h, a comple: of ymptom thathamper differential dia$no i ' 5ltho#$h the di ea ei elf%limitin$, ca e of ne#rolo$ic manife tation andthe =#illain>?arr@ yndrome +ere de cri!ed inFrench 6olyne ia and in ?razil d#rin$ NC

http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#t=abstracthttp://www.nejm.org/doi/full/10.1056/NEJMoa1600651#t=articlehttp://www.nejm.org/doi/ref/10.1056/NEJMoa1600651#t=referenceshttp://www.nejm.org/doi/citedby/10.1056/NEJMoa1600651#t=citedbyhttp://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref1http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref2http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref3http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref5http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#t=abstracthttp://www.nejm.org/doi/full/10.1056/NEJMoa1600651#t=articlehttp://www.nejm.org/doi/ref/10.1056/NEJMoa1600651#t=referenceshttp://www.nejm.org/doi/citedby/10.1056/NEJMoa1600651#t=citedbyhttp://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref1http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref2http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref3http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref5


13/23

epidemic ' ., Becent report from the 9ini try ofDealth of ?razil #$$e t that ca e of microcephalyha"e increa ed !y a factor of appro:imately 2

amon$ ne+!orn in the northea t re$ion of theco#ntry, +hich indicate a po i!le a ociation!et+een NC infection in pre$nancy and fetalmalformation ' .We pre ent a ca e of "ertical tran mi ion of NC ina +oman +ho +a pro!a!ly infected +ith NC innorthea tern ?razil at the end of the fir t trime ter ofpre$nancy' 7#r di c# ion incl#de detail of fetalima$in$ and patholo$ical and "irolo$ic analy e '

CASE REPORTn mid%7cto!er 2 1., a 2.%year%old pre"io# ly healthy

8#ropean +oman came to the Aepartment of6erinatolo$y at the *ni"er ity 9edical ;enter inEL#!lLana, lo"enia, !eca# e of a #med fetal

anomalie ' ince Aecem!er 2 13, he had li"ed and+orked a a "ol#nteer in 0atal, the capital of Bio=rande do 0orte tate' he had !ecome pre$nant atthe end of Fe!r#ary 2 1.' A#rin$ the 13th +eek of$e tation, he had !ecome ill +ith hi$h fe"er, +hich+a follo+ed !y e"ere m# c#lo keletal andretrooc#lar pain and an itchin$, $eneralizedmac#lopap#lar ra h' ince there +a a NCepidemic in the comm#nity, infection +ith the "ir#+a # pected, !#t no "irolo$ic dia$no tic te tin$ +aperformed' *ltra ono$raphy that +a performed at 14and 2 +eek of $e tation ho+ed normal fetal$ro+th and anatomy'

http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref5http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref5http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref5http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref5


14/23

he patient ret#rned to 8#rope at 2< +eek of$e tation' *ltra ono$raphic e:amination that +aperformed at 2 +eek of $e tation ho+ed the fir t

i$n of fetal anomalie , and he +a referred to theAepartment of 6erinatolo$y' 5t that time, he al onoticed red#ced fetal mo"ement ' *ltra ono$raphythat +a performed at 32 +eek of $e tationconfirmed intra#terine $ro+th retardation (e timatedthird percentile of fetal +ei$ht) +ith normal amnioticfl#id, a placenta mea #rin$ 3'. cm in thickne(normal ize) +ith n#mero# calcification , a headcirc#mference !elo+ the econd percentile for$e tation (microcephaly), moderate "entric#lome$aly,and a tran cere!ellar diameter !elo+ the econdpercentile' ?rain tr#ct#re +ere !l#rred, and there+ere n#mero# calcification in "ario# part of the

!rain ( Fi$#re 15 and 1? FIGURE 1 6renatal*ltra ono$raphic ma$e and 6hoto$raph of ;oronal liceof ?rain' )' here +ere no other o!"io# fetal tr#ct#rala!normalitie ' Fetal, #m!ilical, and #terine !loodflo+ +ere normal on Aoppler #ltra ono$raphy'

he clinical pre entation rai ed # picion of fetal "iralinfection' ?eca# e of e"ere !rain di ea e andmicrocephaly, the fet# +a $i"en a poor pro$no ifor neonatal health' he mother ree ted that thepre$nancy !e terminated, and the proced#re +a

#! eently appro"ed !y national and ho pitalethic committee ' 9edical termination of thepre$nancy +a performed at 32 +eek of $e tation'

http://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1600651&iid=f01http://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1600651&iid=f01


15/23

5t the deli"ery, the only morpholo$ic anomaly +a theprominent microcephaly' =enetic con #ltation thatincl#ded a detailed maternal family hi tory re"ealed

no # picion of $enetic yndrome or di ea e ' 5na#top y +a performed, a i mandatory in all ca eof termination of pre$nancy' he mother pro"ided+ritten informed con ent for the p#!lication of thica e report'

METHODSAuto s! an" Centra# $ervous S!ste% &C$S'E(a%ination

5n a#top y of the fet# and placenta +a performed 3day after termination of the pre$nancy, +ith ane:ten i"e amplin$ of all or$an , placenta, and#m!ilical cord' ample +ere fi:ed in 1 K !#fferedformalin and em!edded in paraffin' Fre h ti #e

ample +ere collected for micro!iolo$ic

in"e ti$ation ' ?rain and pinal cord +ere fi:ed in2-K !#ffered formalin for 3 +eek , after +hich ane#ropatholo$ical e:amination +a performed +ithe:ten i"e amplin$ of the !rain and pinal cord'

ection of all ti #e ample +ere tained +ithhemato:ylin and eo in' mm#no tainin$ for $lialfi!rillary acid protein, ne#rofilament, h#man le#kocyteanti$en AB (DE5%AB), ;A3 (to hi$hli$ht cell ), and;A2 (to hi$hli$ht ? cell ) +a performed onrepre entati"e ;0 ample 'E#e)tron Mi)ros)o !


16/23

i #e +a collected from formalin%fi:ed !rain and#nder+ent fi:ation in 1K o mi#m tetro:ide anddehydration in increa in$ concentration of ethanol'

he ample +a then em!edded in 8pon' emithinection (1'4 Om) +ere made, tained +ith 5z#r ,and analyzed !y mean of li$ht micro copy' *ltrathin

ection ( nm) +ere tained +ith #ranyl acetate andlead citrate' n addition, a mall piece of !rain (. mm 3)+a homo$enized in !#ffer' he # pen ion +a thencleared !y lo+% peed centrif#$ation, and the o!tained

#pernatant +a #ltracentrif#$ed directly onto anelectron micro copic $rid +ith the # e of an 5irf#$e(?eckman ;o#lter)' 0e$ati"e tainin$ +a performed+ith 1K pho phot#n$ tic acid' ma$in$ of the #ltrathin

ection and !rain homo$enate +a performed +iththe # e of a 12 %kC 89%14 6l# tran mi ionelectron micro cope ( 87E)'In"ire)t I%%uno*#uores)en)e6araffin%em!edded ection of the fetal !rain ti #eand !rain ti #e of an a#top ied man a a ne$ati"econtrol +ere inc#!ated +ith er#m o!tained from themother of the fet# (dil#tion, 1G1 ), follo+ed !yantih#man $= anti!odie la!eled +ith fl#ore ceini othiocyanate (F ;) (dil#tion, 1G. )' n addition, fetal!rain ti #e +a inc#!ated +ith a er#m o!tained

from a healthy !lood donor, a +ell a +ith F ;%la!eled antih#man $= anti!odie only'Mi)ro+io#o,i) Investi,ationB05 +a e:tracted from 1 m$ of the placenta, l#n$ ,heart, kin, pleen, thym# , li"er, kidney , and


17/23

cere!ral corte: +ith the # e of a B zol 6l# B05p#rification kit ( hermo Fi her cientific)' Beal%timeB %6;B for the detection of NC B05 (0 .) and

one% tep B %6;B for the detection of the en"elope%protein codin$ re$ion (3 !p) +ere performed ade cri!ed pre"io# ly' -,< n addition, ne:t%$eneration

eencin$ +a performed in ample of fetal !rainti #e +ith the # e of on orrent ( hermo Fi her

cientific) and =eneio# oft+are, "er ion ' ' 'Bead from !oth r#n +ere com!ined and mapped tothe reference eence ( NC 9B- E; 2.2 )+ith the # e of defa#lt mea #re ' For phylo$eneticanaly i , complete%$enome NC eence +ere# ed, and m#ltiple eence ali$nment (;l# talW)+ere performed' 5 nei$h!or%Loinin$ phylo$enetic tree(= BP=P model) +a con tr#cted, +ith the # e ofthe 98=5 oft+are y tem, to ho+ thephylo$enetic relation hip ' he n#cleotide eence

of NC that +a o!tained in thi t#dy ha !eendepo ited in =en?ank #nder acce ion n#m!erN*.2-


18/23

RESU-TSAuto s! an" $euro at.o#o,i)a# Fin"in,s

he fetal !ody +ei$ht +a 14- $ (.th percentile), thelen$th 42 cm (1 th percentile), and the headcirc#mference 2 cm (1 t percentile)' he onlye:ternal anomaly that +a noted +a microcephaly'

he placenta +ei$hed 2 $, re #ltin$ in a placental>fetal +ei$ht ratio of '13 (Q3rd percentile)'9acro copic e:amination of the ;0 re"ealedmicrencephaly +ith a +hole%!rain +ei$ht of


19/23

a tro$lio i +a pre ent +ith focal a trocytic o#t!#r tinto the #!arachnoid pace, mo tly on the con"e:ityof the cere!ral hemi phere ( Fi$#re 2; )' 5cti"ated

micro$lial cell and ome macropha$e e:pre in$DE5%AB +ere pre ent thro#$ho#t mo t of the cere!ral$ray and +hite matter ( Fi$#re 2A )' cattered mildperi"a c#lar infiltrate compo ed of cell and ome? cell +ere pre ent in the #!cortical +hite matter(Fi$' 1 in the #pplementary 5ppendi: )' hecere!ell#m, !rain tem, and pinal cord ho+edneither inflammation nor dy trophic calcification ' he!rain tem and pinal cord ho+ed Walleriande$eneration of the lon$ de cendin$ tract , e peciallythe lateral cortico pinal tract, +herea a cendin$dor al col#mn +ere +ell pre er"ed ( Fi$#re 28 )'

ndirect imm#nofl#ore cence re"ealed $ran#larintracytopla mic reaction in de troyed ne#ronal

tr#ct#re , +hich pointed to a po i!le location of the

"ir# in ne#ron ( Fi$#re 2F , and Fi$' 1 inthe #pplementary 5ppendi: )' Di tolo$ic e:aminationof the placenta confirmed focal calcification in "illiand decid#a, !#t no inflammation +a fo#nd' here+ere no rele"ant patholo$ical chan$e in other fetalor$an or in the #m!ilical cord or fetal mem!rane 'Fetal karyotypin$ +ith the # e of microarraytechnolo$y ho+ed a normal 4 RM (male) profile'E#e)tron Mi)ros)o !

5ltho#$h analy i of the #ltrathin ection of the !rainho+ed poorly pre er"ed !rain ti #e +ith r#pt#red

and ly ed cell , cl# ter of den e "ir# %like particle

http://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1600651&iid=f02http://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1600651&iid=f02http://www.nejm.org/doi/suppl/10.1056/NEJMoa1600651/suppl_file/nejmoa1600651_appendix.pdfhttp://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1600651&iid=f02http://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1600651&iid=f02http://www.nejm.org/doi/suppl/10.1056/NEJMoa1600651/suppl_file/nejmoa1600651_appendix.pdfhttp://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1600651&iid=f02http://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1600651&iid=f02http://www.nejm.org/doi/suppl/10.1056/NEJMoa1600651/suppl_file/nejmoa1600651_appendix.pdfhttp://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1600651&iid=f02http://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1600651&iid=f02http://www.nejm.org/doi/suppl/10.1056/NEJMoa1600651/suppl_file/nejmoa1600651_appendix.pdf


20/23

of appro:imately . nm in ize +ere fo#nd indama$ed cytopla mic "e icle ' =ro#p of en"eloped

tr#ct#re +ith a !ri$ht interior +ere al o detected' 5t

the periphery of #ch $ro#p , the remain ofmem!rane co#ld !e een' 0e$ati"e tainin$ ofhomo$enized !rain re"ealed pherical "ir# particlemea #rin$ 42 to .4 nm +ith morpholo$iccharacteri tic con i tent +ith "ir# e of the

Fla"i"iridae family ( Fi$#re 3 FIGURE 08lectron 9icro copy of *ltrathin ection of Fetal ?rain and

tainin$ of a Fla"i"ir# %like 6article' )'Mi)ro+io#o,i) Investi,ation6o iti"e re #lt for NC +ere o!tained on B %6;Ba ay only in the fetal !rain ample, +here

'.S1 - "iral B05 copie per milli$ram of ti #e +eredetected' n addition, all a#top y ample +ere te tedon 6;B a ay and +ere fo#nd to !e ne$ati"e forother fla"i"ir# e (den$#e "ir# , yello+ fe"er "ir# ,We t 0ile "ir# , and tick%!orne encephaliti "ir# ),alon$ +ith chik#n$#nya "ir# , lymphocyticchoriomenin$iti , cytome$alo"ir# , r#!ella "ir# ,"aricella>zo ter "ir# , herpe imple: "ir# ,par"o"ir# ?1 , entero"ir# e , and To'oplas%a

"ondii ( a!le 2 in the #pplementary 5ppendi: )' 5 complete NC $enome eence (1 ,< <n#celotide ) +a reco"ered from !rain ti #e'6hylo$enetic analy i ho+ed the hi$he t identity( '-K) +ith the NC train i olated from a patient

http://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1600651&iid=f03http://www.nejm.org/doi/suppl/10.1056/NEJMoa1600651/suppl_file/nejmoa1600651_appendix.pdfhttp://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1600651&iid=f03http://www.nejm.org/doi/suppl/10.1056/NEJMoa1600651/suppl_file/nejmoa1600651_appendix.pdf


21/23

from French 6olyne ia in 2 13 (N -- - 1) and NCdetected in ao 6aolo, ?razil, in 2 1. (N*321 3 ),follo+ed !y a train i olated in ;am!odia in 2 1

( 0<


22/23

and no patholo$ical chan$e +ere detected in anyother fetal or$an apart from the !rain, +hich

#$$e t a tron$ ne#rotropi m of the "ir# '

he localization of imm#nofl#ore cence i$nal andthe morpholo$ic appearance of the calcification ,+hich re em!led de troyed ne#ronal tr#ct#re ,indicate a po i!le location of the "ir# in ne#ron '

he con eent dama$e mi$ht ca# e arre tedde"elopment of the cere!ral corte: at the em!ryonica$e of appro:imately 2 +eek ' 14 he mechani min"ol"ed in the ne#rotropi m of NC i c#rrently notclear' he a ociation !et+een NC infection andfetal !rain anomalie +a al o noted !y findin$ onelectron micro copy that +ere con i tent +ith NCdetection in the fetal !rain' Aen e particle con i tent+ith NC +ere een in dama$ed endopla micretic#l#m' =ro#p of en"eloped tr#ct#re +ith a!ri$ht interior re em!lin$ the remain of replication

comple:e that are characteri tic offla"i"ir# e 1.,1 indicate "iral replication in the !rain'he findin$ on electron micro copy #$$e t a

po i!le per i tence of NC in the fetal !rain,po i!ly !eca# e of the imm#nolo$ically ec#remilie# for the "ir# ' he n#m!er of "iral copie that+ere detected in the fetal !rain +ere #! tantiallyhi$her than tho e reported in the er#m o!tained fromad#lt NC%infected patient 1- !#t imilar to tho ereported in emen ample ' 1<

he complete $enome eence of NC that +areco"ered in thi t#dy i con i tent +ith theo! er"ation that the pre ent train in ?razil ha

http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref14http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref15http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref17http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref18http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref14http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref15http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref17http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref18


23/23

emer$ed from the 5 ian linea$e' 1 he pre ence oft+o maLor amino acid #! tit#tion po itioned innon tr#ct#ral protein 0 1 and 0 4? pro!a!ly

repre ent an accidental e"ent or indicate a proceof e"ent#al adaptation of the "ir# to a ne+en"ironment' F#rther re earch i needed to !etter#nder tand the potential implication of the eo! er"ation ' t i likely that the rapid pread of NCaro#nd the $lo!e +ill !e a tron$ impet# forcolla!orati"e re earch on the !iolo$ic propertie ofthe "ir# , partic#larly ince the ri k of ne#rotropic andterato$enic "ir# infection place a hi$h emotionaland economic !#rden on ociety'
http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref19http://www.nejm.org/doi/full/10.1056/NEJMoa1600651#ref19