The first outbreak of measles virus caused by imported genotype D8 in Jiangsu province of China

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brazjinfectdis2019;23(1):66–69

w w w . e l s e v ie r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Brief

communication

The

ﬁrst

outbreak

of

measles

virus

caused

by

imported

genotype

D8

in

Jiangsu

province

of

China

Xiuying

Deng,

Ying

Hu,

Peishan

Lu,

Ming-hao

Zhou,

Hongxiong

Guo

∗ JiangsuProvincialCenterforDiseaseControlandPrevention,Nanjing,China

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Articlehistory:

Received5November2018 Accepted27February2019 Availableonline12March2019

Keywords:

Measlesvirus ImportedD8genotype Outbreak

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HerewereportedtheoutbreakofmeaslescasescausedbythegenotypeD8measlesvirusfor theﬁrsttimeinJiangsuprovinceinChina,whichwaspossiblyimportedbyaforeignstudent fromLaos.Throatswabspecimenswerecollected,andusedtoisolatevirus.634-bpfragment oftheNgeneand1854-bpfragmentofHgenewereampliﬁedbyreversetranscription-PCR andsequenced,respectively.Phylogeneticresultsindicatedthattheybelongedto geno-typeD8measlesvirus.FurtherepidemiologyinvestigationshowedthattheadultswithD8 measlesvirusinfectiondidnotreceivemeaslesvaccinebeforehavingmeasles.InChina, almostallD8genotypeMeVonlyinfectedthosepopulationwithoutreceivingmeasles vac-cineimmunization.Therefore,itisstillnecessarytoimplementthesupplementactivityof measlesimmunizationtargetadultwithimmunitygap.

Hereinwereporttheoutbreakofmeaslescausedbythe geno-type D8 measles virus (MeV) for the ﬁrst time in Jiangsu provinceinChina,whichwaspossiblyimportedbyaforeign studentfromLaos.Throatswabspecimenswerecollectedand usedtoisolatethevirus.A 634-bpfragmentofthe Ngene and1854-bp fragmentofHgene wereampliﬁedbyreverse transcription-PCRandsequenced,respectively.Phylogenetic resultsindicatedthattheybelongedtogenotypeD8MeV. Fur-therepidemiologicalinvestigationshowedthatadultswithD8 MeVinfection hadnotbeenvaccinated againstmeasles.In China,almostallcasesofD8genotypeMeVinfectionoccurred inpatientswithnopreviousmeaslesvaccination.Therefore, itisnecessarytooffermeaslesvaccinationforadultswhoare immunized.

∗ _{Corresponding}_author.

E-mailaddresses:guohongxiong@jscdc.cn,hongxiongguo@gmail.com(H.Guo).

Countriesallovertheworldhaveadoptedgoalsformeasles eliminationbyorbefore2020.1_Toward_that_end,_China govern-ment implemented measles supplementary immunization activity inthewholecountry in2010,andthe incidenceof measlesdecreaseddramatically,reachingthelowestreported levelin2012.2,3_However,_a_nationwide_resurgence_of_measles occurred primarily amongyoung unvaccinated childrenin 2013.4 _Both_before_and_after_resurgence _of_measles,_H1_has been the predominant strain in China, although only a few imported D8, D9, and vaccine-associated strains were found.5–7

JiangsuProvince, locatedinthe east ofChina,isoneof the highlyeconomicallydevelopedregions inChina.Ithas nearly80millionpermanentresidentsandmigrants.Over95%

https://doi.org/10.1016/j.bjid.2019.02.003

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MVs/HongKong,CHN/05.17/D8 MVi/Chiba.JPN/32.16/3/D8 MVi/Amsterdam.NLD/41.17/D8 MVi/Cheonan.KOR/38.16/2/D8 MVi/BuenosAires.ARG/13.18/D8 MVs/HongKong.CHN/08.17/D8 MVs/HongKong.CHN/46.12/D8 MVs/HongKong.CHN/18.11/D8 MVs/HongKong.CHN/10.14/1/D8 KJ994346.1/zhongshan20140526/D8 MVi/Menglian.Yunnan.CHN/47.09/D11 MVi/Victoria.AUS/16.85/D7 MVi/Victoria.AUS/12.99/D9 MVi/Illinoise.USA.99/D7 MVi/Illinoise.USA/0.89/1/D3 MVi/Bangkok. THA/0.93/1/D5 MVi/Palau/0.93/D5 MVi/Johannesburg.ZAF/0.88/1/D2 MVi/Kampala.UGA/51.00/1/D10 MVi/Bristol.GBR/0.74/D2 MVi/New Jersey:USA/0.94/1/D6 MVi/Hunan.CHN/0.93/7/H1 Chin9322/H1a Chin9475/H1b MVi/Beijing.CHN/0.94/1/H2 MVi/Berkeley.USA/0.83/G1 MVi/Amsterdam.NLD/49.97/G2 MVi/Gresik.IDN/17.02/G3 MVi/Maryland.USA/0.77/C2 MVi/Maryland.USA/0.54/A MVi/Libreville.GAB/0.84/B2 MVi/Yaounde.CMR/12.83/B1 MVi/New York. USA/0.94/B3

MVi/Ibadan.NGA/0.97/1/B3 94 77 83 100 93 80 80 93 96 Shanghai-191/China-vaccine MVi/Erlangen.DEU/0.90/C2 MVi/Tokyo.JPN/0.84/C1 MVi/Goettingen.DEU/0.71/E MVs/Madrid.ESP/0.94(SSPE)/F MVi/Montreal.CAN/0.89/D4 MVs/Beijing.CHN/31.13/03/D8 MVi/Beijing.CHN/20.13/03D8 MVi/WesternAustralia.AUS/2.18/D8 MVi/Jiangsu.CHN/42.17/1/D8 MVi/Jiangsu.CHN/42.17/2/D8 MVs/HongKong.CHN/24.14/1D8 MVi/Manchester.GBR/30.94/D8 94 94 76 99 98

Fig.1–Phylogenetictreebasedonthenucleotideprotein(N)genesequencesofvariousstrainsofthemeaslesvirus.The

evolutionarydistancewascalculatedusingKimura’stwo-parametermethod,andthetreewasplottedusingthe

neighbor-joiningmethod.Numbersateachbranchindicatethebootstrapvaluesoftheclusterssupportedbythatbranch, onlymorethan75%ofbootstrapvalueisindicated.Jiangsucaseswerecircledwithrectangleline.

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braz j infectdis.2019;23(1):66–69 99 99 100 100 100 93 96 95 98 79 97 100 100 100 100 78 100 95 0.005 Victoria.AUS/16.85/D7 MVi/Minois. USA/50.99/D7 Montreal. CAN/89/D4 Manchester. UNK/30.94/D8 MVi/Jiangsu.CHN/42.17/1/D8 MVi/Jiangsu.CHN/42.17/D8 Palau.BLA/93/D5 Illinois. USA/89/1D3 Victoria.AUS/12.99/D9 New Jersey. USA/94/1/D6 Bristol. UNK/74/D1 Johannesburg.SOA/88/1/D2 Mvi/Kampala. UGA/51.00-1/D10 Tokyo.JPN/84/K/C1 Maryland. USA/77/C2 Goettingen.DEU/71/E Edmonston-wt.USA/54/A Shanghai-191/China-vaccine MVs/Madrid.SAP/94/F Libreville. GAB/84/B2 Yaounde.CAE/12.83/B1

New York. USA/94/B3 Berkeley.USA/83/G1 Amsterdam.NET/49.97/G2 Gresik.INO/17.02/G3 Beijing.CHN/94/1/H2 China94-7/H1b China93-4/H1a China93-7/H1c

Fig.2–Phylogenetictreebasedonthehemagglutininprotein(H)genesequencesofvariousstrainsofthemeaslesvirus.

TheevolutionarydistancewascalculatedusingKimura’stwo-parametermethod,andthetreewasplottedusingthe

neighbor-joiningmethod.Numbersateachbranchindicatethebootstrapvaluesoftheclusterssupportedbythatbranch, onlymorethan75%ofbootstrapvalueisindicated.Jiangsucaseswerecircledwithrectangleline.

ofthechildrenarevaccinatedagainstmeasles.Nonetheless, measlesresurgedin2014,andsubsequentlydeclinedrapidly tothelevel before2013until2016.Molecularepidemiology surveillanceshowedthatonlyH1agenotypewascirculating inJiangsuprovince.

BetweenSeptember22andOctober18,2017twomeasles caseswerereportedbyNantongPrefectureCenterforDisease ControlandPrevention(NPCDC).Case1:onOctober15,2017, a31-yearoldfemalecollegeteacherpresentedwithfever.Two dayslater,rashesappeared,followed bycough, rhinorrhea, sneezing,andwasdiagnosedasmeaslesinhospitalX.

Case2: on October 13, 2017, a36-year old female jani-tor,workingatthe outpatienttransfusion roominhospital Xpresentedwithfever,progressingwithrashesandcoughon October17,andwasdiagnosedasmeasles.

Throat swab and blood specimens were collected on October 17 and October 18,respectively. IgM antibodyand real-time ﬂorescence PCR for measles and rubella were performedatNPCDC.IgMantibodyinserumandnucleicacid inswabturnedoutpositiveformeaslesvirus.Subsequently, swabspecimensweretransportedtoJiangsuProvinceCenter forDiseaseControlandPrevention(JSCDC)forviralisolation

andgenotypeidentiﬁcation.TheVero/SLAMcellline(African green monkey kidney cells human signaling lymphocyte activation molecule)wasusedfortheisolationofMeV,and theinfectedcellswereharvestedwhenthecytopathiceffect (CPE) was visible in more than 75% of the cell layer. The QIAamp® ViralRNAMiniKit(Qiagen,HildenGermany)was usedtoextractMeVnucleicacidaccordingtothe manufac-turer’sinstructions.Reversetranscriptionampliﬁcationwas performed usingpreviouslydescribed primers toamplifya 634-bp fragment ofthe Ngene and a1854-bp fragmentof theHgene,8_which_included_enough_length_fragment recom-mended forgenotyping.ThePCRproductsweresequenced using ABI3730DNASequencer(AppliedBiosystems,Foster City, CA, USA) at Sagon Biotech (Shanghai, China) using directionalprimers.ThesequenceswereeditedusingBioedit software,thenanalyzedusingMEGA7.0software.

Furtherepidemiological investigationshowed thatthese twocaseshadnohistoryoftravelingtoothercountriesand hadnotreceivedmeaslesvaccination.Aforeignfemale stu-dent from Vientiane (the capital and largest city of Laos) hadbeentoChinaonSeptember12,arrivingtoNantongon September14.AsofSeptember22,shedevelopedfeverand

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rashesandwenttoHospitalXforcare.However,nofurther informationcouldbeobtained.Nonetheless,therewasa pos-sibilityofmeaslestransmissionbetweenthisstudentandthe twocases described above. Case1was the teacher ofthis student incollege. Case2 had been workingat hospitalX whentheforeignstudentwenttohospitalXforcare.The fur-therphylogeneticanalysisshowedthemeaslesvirusesinthis eventbelongtoD8genotype(Figs.1and2).Theyshare99% identitywiththeNgenesequences(450bp)ofmeaslesvirus fromJapan,Australian,Argentina,England,Netherlands,and ChinaHongkongandwiththeHgenesequences(1854bp)of itfromtheUnitedKingdom,Canada,USA,andAustralia.

Asfarasweknow,thisistheﬁrstmeaslesoutbreakcaused byimportedD8genotypeinJiangsuprovince,andthefourth inChina.2,5,9 _Further _{epidemiological} _{investigation} _showed thatneitherofthetwopatientsreportedhereinhadreceived measlesvaccination.TheﬁrstD8casewasaneight-month oldchildfrom Shanghaiin2012,withnoprevious measles vaccination,5_and_the_second_outbreak_was_in_Beijing_in_2013, withtwoadultcases,forwhomnoinformationonmeasles vaccinationcouldbegathered.2 _All_of_these_reports_suggest thatanimmunitygapamongallimportedD8genotypecases, whichis stillanimportantfactor fortransmitting measles virus. It is therefore necessary to implement supplement activityofmeaslesimmunizationtargetadultwithimmunity gap.

Populationdensityisamajordeterminantofattackrates andtransmission ofmeaslesvirus.10,11 InChina,almost of allimportedmeaslescasesoccurredineconomically devel-opedregionsandborderregions.12–14_Frequent_migration_and higherpopulationdensitymaketheseregionsmore vulnera-blethanothersinChina,asalladultsgotimportedmeasles virusinfectioninvenueswithhigherpopulationdensitysuch asschool,hospital,andfabricmarket.Therefore,more atten-tionshouldbedrawntomeaslessurveillanceinregionsand venueswithhighpopulationmigrationanddensity,especially inepidemicseasons.

Conﬂicts

of

interest

Theauthorsdeclarenoconﬂictsofinterest.

Acknowledgment

WethankallstaffattheDepartmentofExpandedProgram onImmunizationofNantongPrefectureCenter forDisease

Control and Prevention for making this investigation pos-sible.ThisstudywaspartlysupportedbyJiangsuProvincial High-LevelTalentsProgramsinHealth(LGY2016021).

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1.DabbaghA,PatelMK,DumolardL,etal.Progresstowards regionalmeasleseliminationworldwide,2000–2016.Wkly EpidemiolRec.2017;92:649–60.

2.ChenM,ZhangY,HuangF,etal.Endemicandimported measlesvirus-associatedoutbreaksamongadults,Beijing, China,2013.EmergInfectDis.2015;21:477–9.

3.MaC,LiF,ZhengX,etal.Measlesvaccinecoverageestimates inanoutbreakthreeyearsafterthenation-widecampaignin China:implicationsformeasleselimination,2013.BMCInfect Dis.2015;15:1–8.

4.LiS,MaC,HaoL,etal.Demographictransitionandthe dynamicsofmeaslesinsixprovincesinChina:amodeling study.PLoSMed.2017;14:e1002255.

5.LiS,QianX,YuanZ,etal.Molecularepidemiologyofmeasles virusinfectioninShanghaiin2000-2012:theﬁrstappearance ofgenotypeD8.BrazJInfectDis.2014;18:581–90.

6.XuS,ZhangY,RivaillerP,etal.Evolutionarygeneticsof genotypeH1measlesvirusesinChinafrom1993to2012.J GenVirol.2014;95:1892–9.

7.ZhangY,WangH,XuS,etal.Monitoringprogresstoward measleseliminationbygeneticdiversityanalysisofmeasles virusesinChina2009–2010.ClinMicrobiolInfect.

2014;20:O566–77.

8.MaguranoF,FortunaC,MarchiA,etal.Molecular epidemiologyofmeaslesvirusinItaly,2002–2007.VirolJ. 2012;9:1–9.

9.YanR,HeB,YaoF,etal.Investigationofameaslesoutbreak causedbygenotypeD8virusinPinghucityofZhejiang province,2017.ChinJEpidemiol.2018;39:333–6.

10.SmithsonR,IrvineN,HuttonC,etal.Explainingseasonal ﬂuctuationsofmeaslesinNigerusingnighttimelights imagery.Science.2011;334:1424–7.

11.FalkSJ,GuoLY,SekulicN,etal.Long-termmeasles-induced immunomodulationincreasesoverallchildhoodinfectious diseasemortality.Science.2015;348:694–9.

12.FangX,SunJ,ZhangY,etal.Theﬁrstmeaslesoutbreak causedbyimportedgenotypeD9measlesvirusinShandong Province,China,2013.JpnJInfectDis.2014;67:300–3.

13.PangY-K,LiL-Q,DingZ-R,etal.Investigationonanoutbreak ofmeaslescausedbynewvirus(d11genotype)importedfrom Myanmar.ChinJEpidemiol.2014;32:17–9.

14.ZhaoZ,ZhouR,YuW,LiL,LiQ,HuP.Measlesoutbreak preventionandcontrolamongadults:lessonsfroman importationoutbreakinYunnanprovince,China,2015.Hum VaccinImmunother.2018;14:881–6.