Sporadic human cutaneous anthrax outbreak in Shaanxi Province, China: report of two cases from 2018

brazjinfectdis2020;24(1):81–84

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

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Brief

communication

Sporadic

human

cutaneous

anthrax

outbreak

in

Shaanxi

Province,

China:

report

of

two

cases

from

2018

Yuanyuan

Liu

_,

_Yongqin

_Li

_,

_Qiaoxia

_Wang

_,

_Jianjun

_Fu

_,

_Fanpu

_Ji

a_{TheAffiliatedXi’anCentralHospitalofXi’anJiaotongUniversity,DepartmentofInfectiousDiseases,Xi’an,China}

b_{TheSecondAffiliatedHospitalofXi’anJiaotongUniversity,DepartmentofInfectiousDiseases,Xi’an,China}

c_{Xi’anJiaotongUniversity,TheSecondAffiliatedHospital,National&LocalJointEngineeringResearchCenterofBiodiagnosisand}

Biotherapy,Xi’an,China

d_{MinistryofEducationofChina,Xi’anJiaotongUniversity,KeyLaboratoryofEnvironmentandGenesRelatedtoDiseases,Xi’an,China}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received24August2019 Accepted8December2019 Availableonline9January2020

Keywords:

Bacillusanthracis

Cutaneousanthrax Vaccination

a

b

s

t

r

a

c

t

China’scompulsoryannuallivestockanthraxvaccinationpolicyhasremarkablyreducedbut notcompletelyeradicatedhumananthraxinfections.Hereinwedescribeasporadichuman cutaneousanthraxoutbreakinvolvingtwocasesin2018inShaanxiProvince,bothinvolving herdsmanwhodealtwithunvaccinatedandpotentiallysickcattle.Bothpatientsshowed

Bacillusanthracis-positiveblistersmearandblood culture.Treatmentwithpenicillinwas

followedbyuneventfulrecoveryforboth.Thepromptperformanceoftheprophylactic mea-suressuccessfullyinterruptedthefurthertransmissionofthissporadichumancutaneous anthraxoutbreak.

©2019SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.Thisis anopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Anthraxisanacuteinfectiousdiseasecausedbythe Gram-positiveBacillus anthracis, spore-formingbacterium. Annual estimatesofcasesworldwiderangefrom20,000to100,000, anditisstillconsideredamajorpublichealththreatinAfrica, theMiddleEast,SouthAmerica,centralAsiaandHaiti.1

In China, a total of 3379 human anthrax cases were reported between 2005 and 2014.2 _{Although these cases}

involvedindividualsacrossallprovinces–representingvastly differentphysiographicfeaturesintermsoflandcover,

alti-∗ _{Correspondingauthorat:DepartmentofInfectiousDiseases,TheSecondAffiliatedHospitalofXi’anJiaotongUniversity,157XiWuRoad,}

Xi’an710004,ShaanxiProvince,China.

∗∗ _{Correspondingauthorat:DepartmentofInfectiousDiseases,TheAffiliatedXi’anCentralHospitalofXi’anJiaotongUniversity,161Xi}

WuRoad,Xi’an710004,ShaanxiProvince,China.

E-mailaddresses:fjianj@163.com(J.Fu),jifanpu1979@163.com,infection@xjtu.edu.cn(F.Ji).

1 _{Theseauthorscontributedequallytothismanuscript.}

tude, climate,seasonality, animalhusbandry practices and topsoilfeaturesaswellashumandensityandspatial aggrega-tion–nearlyall(97.7%)weresimilarlyofthecutaneousform.2,3

Herein wereporttwonewcasesofcutaneousanthrax that occurred inShaanxiProvincein2018,describingtheirearly diagnosis and successfultreatment, whichinterrupted the furthertransmissionofthisinfectiousdiseaseintheregion.

Themedicalrecordsforthetwo2018casesofcutaneous anthrax in ShaanxiProvincewere reviewed. In bothcases,

https://doi.org/10.1016/j.bjid.2019.12.002

1413-8670/©2019SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

82

Fig.1–HumancutaneousanthraxinPatient1.A–B)Severeedemaontherightforearm,withmultiplebullaeandacentrally locatedblackhemorrhagiceschar;C)blistersonthedorsalandproximalsidesoftheindexfinger;D)gray-whiterough coloniesgrownonbloodagarmediumfor24haftersmearofthedischargefluid;E)bloodcultureswerepositiveand identifiedasBacillusanthracis;F–G)regressionoftheskinlesionafterpenicillintreatment.

the diagnosisof anthraxhad been based uponthe clinical aspectofthecutaneouslesions,epidemiologicaldata (includ-ing occupation and history of exposureto potentially sick animalsoranimalproducts),andpositivemicroorganism cul-tures(inbothblisterdischargeandblood).

Patient1# _{isa42-year-oldmanwho was acattledealer}

fromtheZhongnanvillageintheQinlingmountainsandwas admittedinearlySeptember2018.Thepatientcomplainedof apainlessredlesionontherightforearmthathadbeen fol-lowedbydevelopmentoflocalizedsoresandswellingforfour days.Onedaypriortothehospitalvisit,thepatientdescribed experiencingprogressivemalaise,confusion,andanintense fever(40◦C).

Physicalexaminationrevealedsevereedema,multiple bul-laeandacentralblackhemorrhagicescharprotrudingoutof theskin(5cm×6cm)onthe rightforearm(Fig.1A,B), vis-ibleindurated escharonthe dorsal and distalsidesofthe

rightindexfinger(Fig.1C),andbilateralaxillarylymphnode enlargement.

Laboratory test showed white blood cell count at 11.8×109_{/L(normallimits4.5–10×10}9_{/L).Cytologysmearof}

dischargefrom variouslesionsoftherightforearmshowed Gram-positiverodsinall(Fig.1D).Cultureofbothdischarge andbloodshowedpositivityforGram-positivebacteria, fur-theridentifiedasB.anthracis(Fig.1E).Hewasdiagnosedwith cutaneousanthraxandisolated,andreceivedpenicillin treat-ment for15 days, along with5mgdexamethasoneforfive days.Hissymptomswentintoremission(Fig.1F,G).

Patient 2# _{is a 27 year-old man who was a partner of}

patient1andhadperformedbutcheringofacowalongside. Hepresentedtoourhospitaltwodaysafterthefirstcase, com-plaining ofrightindexfingeredema.Thepatientdescribed havingnoticedasmall,painlessredlesionontherightfinger threedaysprior.Onexamination,therewasa2×1.5cm

hem-brazj infect dis.2020;24(1):81–84

83

Fig.2–HumancutaneousanthraxinPatient2.A)Cutaneousanthraxsymptomofblackescharandedemaontheright indexfinger;B)Regressionoftheskindamageafterpenicillintreatment;C)bloodcultureswerepositiveandidentifiedas

Bacillusanthracis.

orrhagicbulla,withswollenskinsurrounding anindurated escharonthedorsal and proximalsidesoftherightindex finger(Fig.2A).Laboratorytestsshowednormalwhiteblood cellandbiochemicalparameters.Bloodanddischargeculture showedpositivityforB. anthracis(Fig.2C). Thepatientwas immediatelysegregatedandprescribedpenicillinfor10days. Theswellingimprovedandthepatientrecovereduneventfully (Fig.2B).

Inadditiontosegregatingand treatingthetwopatients, ourstaffimmediately traveledtothe presumedlocation of exposure(theslaughterhousewhichservedthreenearby vil-lages,includingafarmandseveralhouseholdsmaintaining free-ranginglivestock),whereB.anthraciswasfoundonthe choppingboard.Uponalertingthemunicipalhealthbureau and relevantepidemic preventiondepartments,emergency measureswereputintoplacetopreventspreadofthis dis-ease. The slaughterhouseunderwent rigorous disinfection. Furthermore,the peoplewho consumedthe beeffrom this slaughterhousewerecontactedandunderwentdetailed phys-ical examination. Again, the other three cattle from the patients’ households, which maintained free-ranging live-stock,werekilledandburiedintact.Thepromptperformance oftheseprophylacticmeasuressuccessfullyinterruptedthe furthertransmissionofthisinfectiousdiseaseinthefollowing 10months.

Anthraxisaprimaryacutezoonoticinfectioncausedbythe Gram-positive, spore-forming bacteriumB. anthracis, which exists intwo forms: spore and vegetative.3 _{The spore can}

resistphysicalstressandremainviableinsoilfordecades.3

Althoughanthraxisararedisease,inoculationwiththe bac-teriumleadstodeathin20% ofcaseswhennottreatedon time.4_{Cutaneousanthraxistheleastfataltype,beingcaused}

mainlyby hostreactions to the bacterialcapsule and tox-ins.

Human cutaneous anthrax mainly occurs in the body areas directly exposed to the bacterium, commonly being head,neck,andupperextremities.Typicalcasesbeginwith a painless carbuncle that rapidly becomes necrotic, pos-sibly influencing the surrounding areas and often being accompaniedbyinflammationofregionallymphnodes.4_The

initialskin lesion is a painless inflammatorypapule, with an itchy or burning sensation. Next, blisters or pustules form,beingsurroundedbyrigidnon-sagedema.Thenecrotic lesionsubsequentlyrupturesandacarbonaceousblackscab

forms,surrounded bysatellitelesions,suchas blistersand pustules.5,6

Climateisoneofthemainfactorsofanthraxoutbreak.7

InChina,mosthumananthraxcaseshaveoccurredin west-ernregionsandincidencepeaksinthedrymonthofAugust.2

TheQinlingmountainsretardairflowandinhibitthemarine currentfromthesouth,makingthenorthernclimateofthis regiondrywithespeciallyhightemperaturesinthesummer. Thetwocasesofcutaneousanthraxdescribedhereinoccurred inlateAugust;atthattimeofyear,thetemperatureinQinling isbetween22–39◦C,withonlyeightdaysoflightrainorshower (Fig.S1).Thisclimaticconditionissuitableforthesurvivaland reproductionofB.anthracis.8

Duringtheperiodof2005–2014,86.7%ofhumananthrax cases in China involved farmers and herdsmen, and rural casesaccountedfor92.4%ofallcases.2_{Indeed,accordingto}

theWorldHealthOrganization,cattlearethemajorsourcefor humananthrax,4andthenumberofcattleslaughtered annu-allyinChinareportedlyincreasedfrom1980to2013.Bothour patientsinfectedwithanthraxwerefarmersandcattle deal-ers,whodealwithcattleextensivelyandhaveahigherriskof exposuretopotentiallysickanimals.

Immediatelyafterourpatientswerediagnosed,ourstaff went to the presumedlocation ofinfection and confirmed thepresenceofB.anthracis.Theoverallresponsetothetwo casesofanthrax–segregatingpatientsandinitiatingtimely treatment, rigorously disinfectingthe infectious focus, and destroyinganyotherpossiblyillcattle–almostcertainlykept othersfrominfection.

The live attenuated Sterne strain is the most widely used vaccine.9 _{Livestock anthrax vaccinationisa proactive}

approachforpreventingtheepidemicspreadofthisdisease, which is the most effective method to control anthrax in endemic regions, and when combined withimprovements inoccupationalsafetycontributestoanotablereductionin incidenceamongbothhumansandanimals.9,10 _Incontrast,

a study inGeorgiaindicated thatwhen the country ended its policy ofcompulsory annual livestockanthrax vaccina-tion,theoverallriskofhumananthraxincreased>5-fold.11

TheChinesegovernmentrequiresmandatoryanthrax vacci-nationoflivestock.Ifeconomicfactorsleadtounvaccinated livestock and the slaughter of potentially sick cattle, an anthraxepidemiccanoccur.Itisimportantforthe govern-mentalinstrumentalitiestocontinuetoconductquarantined

84

inspectionduringthepurchase,transportation,slaughterand processing of livestock. In addition, the persons who are engagedinpurchasing,processingand slaughteringanimal productsshouldalsobeinoculatedwiththeB.anthrax vac-cine.

Penicillin istreatment of choicefor cutaneous anthrax, followed by aminoglycosides, such as gentamicin, strep-tomycin, amikacin, etc.12 _{However, B. anthracis has been}

reportedto beresistant tothese antibacterial drugs. Some studies suggest that short-course antibiotic therapy is as effectiveasstandard-durationtherapyincasesof uncompli-catedcutaneousanthrax,andthatsteroidtherapymaynot benecessary,especiallyformildcases.12,13_{Thus,theWorld}

Health Organization has suggestedintramuscular procaine penicillin, oralamoxicillin or penicillin Vfor mild uncom-plicatedcasesofcutaneousanthrax.14_{Forourtwopatients,}

bothblood and discharge culturesshowed B. anthracisand penicillin sensitivity; indeed, penicillin treatment was fol-lowed by uneventful recovery of both. This outcome was achievedinPatient1#_{despitethecombinationof}

dexametha-sonebeingused(withtheintentofrapidlyrelievingtheskin swelling).

Conclusion

Wereporttwocasesofsporadichumancutaneousanthrax outbreakinvolving cattledealers.Thepromptperformance ofprophylacticmeasuressuccessfullyinterruptedthefurther transmissionofthisoutbreakinthefollowing10months.Our reportemphasizestheimportanceofvaccinationandof tak-ingmeasuresurgentlyinpreventinganthrax incidenceand diseasetransmission.

Grant

support

ThisworkwassupportedbyPersonneltrainingspecialfunds oftheSecondAffiliatedHospitalofXi’anJiaotongUniversity [RC(GG)201501]andtheFundamentalResearchFundsforthe CentralUniversities(No.xzy012019107).

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Author

contributions

Allauthorscollaboratedinthestudydesign;LiuYY,LiYQ,Fu JJ,andJiFPparticipatedindiagnosingandmanagingthesetwo patients;LiuYY,WangQX,andFuJJparticipatedin epidemi-ological investigationincluded slaughterhousedisinfection, physicalexaminationandfollow-upofpeopleconsuming sus-piciouscattle;LiuYY,LiYQ,andJiFPextractedandanalyzed theclinicaldata;LiuYYpreparedthefirstmanuscriptdraft;Fu

JJandJiFPmodifiedthemanuscriptsubsequently;allauthors havereviewedandapprovedthefinalmanuscript.

Acknowledgement

We would like tothank Dr. Wei Shi from Shaanxi Provin-cialCenterforDiseaseControlandPrevention,andDr.Jifeng Liu and QianLi from Xi’anCentre forDiseaseControl and Prevention,fortheirkindhelpincarrying out epidemiolog-icalinvestigation.Wealsowouldliketothankthepatients and suspected exposed populations for their collaboration inconductingepidemiologicalinvestigationsandperforming measurestointerruptthespreadofdisease.

Appendix

A.

Supplementary

data

Supplementary material related to this article can be found,inthe onlineversion,atdoi:https://doi.org/10.1016/j. bjid.2019.12.002.

r

e

f

e

r

e

n

c

e

s

1.Hugh-JonesM.1996–97globalanthraxreport.JAppl Microbiol.1999;87:189–91.

2.LiY,YinW,Hugh-JonesM,etal.Epidemiologyofhuman anthraxinChina,1955–2014.EmergInfectDis.2017;23:14–21.

3.ChenWJ,LaiSJ,YangY,etal.Mappingthedistributionof anthraxinmainlandChina,2005–2013.PLoSNeglTropDis. 2016;10:e0004637.

4.Anthraxinhumansandanimals.Geneva:WorldHealth Organization;2008.

5.GodynJJ,ReyesL,SideritsR,HazraA.Cutaneousanthrax: conservativeorsurgicaltreatment.AdvSkinWoundCare. 2005;18:146–50.

6.Pérez-TanoiraR,RamosJM,Prieto-PérezL,etal.Diagnosisof cutaneousanthraxinresource-poorsettingsinWestArsi Province,Ethiopia.AnnAgricEnvironMed.2017;24:712–5.

7.TimofeevV,BahtejevaI,MironovaR,etal.Insightsfrom Bacillusanthracisstrainsisolatedfrompermafrostinthe tundrazoneofRussia.PLoSOne.2019;14:e0209140.

8.VaccaI.Epidemiology:anthraxthreatenswildlife.NatRev Microbiol.2017;15:515.

9.TurnbullPC.Anthraxvaccines:past,presentandfuture. Vaccine.1991;9:533–9.

10.ShlyakhovEN,RubinsteinE.Humanliveanthraxvaccinein theformerUSSR.Vaccine.1994;12:727–30.

11.KracalikI,MalaniaL,BroladzeM,etal.Changinglivestock vaccinationpolicyalterstheepidemiologyofhumananthrax, Georgia,2000–2013.Vaccine.2017;35:6283–9.

12.ShiehWJ,GuarnerJ,PaddockC,etal.Thecriticalroleof pathologyintheinvestigationofbioterrorism-related cutaneousanthrax.AmJPathol.2003;163:1901–10.

13.LiuDL,WeiJC,ChenQL,etal.Geneticsourcetrackingofan anthraxoutbreakinShaanxiprovince,China.InfectDis Poverty.2017;6:14.

14.EmetM,TortumF,KaragozS,CalbayA.Cutaneousanthrax.J EmergMed.2017;52:240–1.