braz j infect dis.2015;19(6):670–671
www .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
Letter to the Editor
Sentinel site surveillance of nontuberculous mycobacteria pulmonary diseases in Zhejiang, China, 2011–2013
DearEditor,
Theprevalenceofnontuberculousmycobacterial(NTM)infec- tionworldwidehasincreased,andlungisthemostheavily affectedorgan.1BecauseNTMandMycobacteriumtuberculosis (MTB)arebothacid-fastbacilli(AFB),itisdifficulttodistin- guishthemusingtheAFBtestalone,anddrugtreatmentfor NTMistotallydifferentfromanti-tuberculosis(TB)therapy.
ThereisahighincidenceofpulmonaryTBinChina,2butChi- nesehospitalsstillusepositiveAFBtest,clinicalsymptoms, andchest radiographicabnormalities asthe keydiagnostic criteriaforpulmonaryTB.Therefore, thereisahighriskof NTMpulmonaryinfectionbeingmisdiagnosedandincorrectly treated.3Inordertoinvestigatetheprevalence,clinicalchar- acteristicsandriskfactorsofNTMinfectioninpatientswho metChinesepulmonaryTBdiagnosticcriteria,weperformed thisstudyinZhejiangProvince,southeasternChina.
Thisinvestigationwasconductedprospectivelyinsentinel sitesof12countiesinZhejiangfromJanuary2011toDecember 2013.Allthesentinelsitesarepartofalaboratoryandhospital network,theChineseDemonstrationZoneoftheprevention andtreatmentofinfectiousdiseases,whichwassetforsys- tematicsurveillanceofpulmonaryTB.3Thelaboratoriesand hospitalscollectedthesputumsamplesandclinicaldataof HIVnegativesuspectedpulmonaryTBpatientsandperformed mycobacterialcultureandAFBtest.TheAFB-positiveisolates weresenttocentrallaboratory,andfirsttestedusingaCapital- BioMycobacteriumidentificationmicroarray.3,4 Theidentified NTMstrainswere thenfurthertestedbysequencingof16S rRNA,heatshockprotein65(hsp65),andtheRNApolymerase beta-subunit-encoding (rpoB) genes and then compared by BLASTanalysis.NTMpulmonarydiseasewasdiagnosedbased oncriteriaproposedbytheAmericanThoracicSociety(AST) guidelines.5
SPSSversion19.0wasusedforthestatisticalanalyses.The Cochran-Armitagetrendtestwasusedtoevaluatetheannual incidenceofNTM pulmonaryisolates. Thedistributions of smoking,alcoholabuse,bronchiectasis, pulmonaryemphy- sema,chronicbronchitis,andlivingandworkingconditions
betweenmalesandfemaleswerecomparedusingthe2test.
Theindependentriskfactorsaffectingpatientoutcomewas identifiedbylogisticregressionanalysisincludingallpatients.
Resultswereconsideredstatisticallysignificantwhenp-value
<0.05.
Atotal of1953AFB-positive mycobacterialisolateswere cultured from the sputumsamples of1831suspected pul- monary TB patients, whereas 113 NTM strains from 100 patientswereidentified.ElevenpatientsmettheASTbacte- riologicalcriteriaforNTMpulmonarydisease;threepatients hadnoclinicalsymptomsorchestradiographyabnormality, andtheirisolatesmighthavebeencontaminantsortransient colonization;other86patientshadpositiveclinicalsymptoms or chest radiography abnormalities,though the number of respiratoryisolateswereinsufficient.Nineteenpatientshad repeatedlynegativeAFBtestsoftheirsputumbuthadposi- tivecultureresults,noneofthemmetNTMpulmonarydisease diagnosticcriteria.
Microarray biochip identification showed that there were 55Mycobacteriumintracellulare andeightMycobacterium aviumisolates,25 Mycobacteriumkansasii,oneMycobacterium malmoense/szulgai, 16 Mycobacterium abscessus/chelonei, one Mycobacteriumgilvum,fourMycobacteriumfortuitum,andthree NTMwithoutspeciesidentification.Directsequencingwere performed in 106 NTM isolates, and out of those six iso- lateswerenotconsistentwithbiochipidentificationresults, includingthreeMycobacteriummarinum,oneMycobacteriumsp.
JDM601,oneMycobacteriumsmegmatis,andoneM.gilvum.
Thepatientclinical characteristicsareshowninTable1.
Multiplelogisticregressionanalysisdeterminedthathistory ofsteroidusetobetheonlyindependentriskfactoraffect- ingpatientprognosis.Oftheeightpatientsusingsteroids,five received anti-NTMtherapywhiletheother threedied.The localhospitalsdidnotreporttheindicationsordetailsforthe steroidtreatment,makingitdifficulttoexplainthisriskfactor, whichmaybeassociatedwiththetherapyusedforend-stage pneumoniapatients.
TheprevalenceofpulmonaryTBcasesinthe12counties was62.1per100,000in2011,68.6per100,000in2012,59.2per
brazj infect dis.2015;19(6):670–671
671
Table1–Patientclinicalcharacteristics.
Characteristic,N=100 Value
Age, ¯X±SD(years) 58.3±17.1
Sex,female,N(%) 32(32.0%)
BMI, ¯X±SD(kg/m2) 20.5±2.9
Ruralresidents,N(%) 63(63.0%)
Manualworkersorfarmers,N(%) 62(62.0%) Transientpopulation*,N(%) 11(10.5%)
AFBnegative,N(%) 19(19.0%)
Agedmaleruralresidents,N(%) 34(34.0%) Youngtransientmalemanualworkers,N(%) 11(10.5%) Non-smokingagedfemale,N(%) 30(30.0%) Comorbidities,N(%)
Steroiduse‡ 8(8.0%)
Alcoholabuse 6(6.0%)
Smoking* 23(23.0%)
Bronchiectasis* 6(6.0%)
Pulmonaryemphysema* 14(14.0%)
Chronicbronchitis 18(18.0%)
Silicosis 1(1.0%)
Hypertension 8(8.0%)
Livercirrhosis 3(3.0%)
Diabetes 2(2.0%)
Radiographicmanifestation,N(%)
Pulmonarycavities 43(43.0%)
Bilateralinvolvement 47(47.0%)
Receivinganti-TBtherapy,N(%) 72(72.0%) Receivinganti-NTMtherapy,N(%) 19(19.0%) Anti-NTMtherapyduration, ¯X±SD(months) 6.5±6.6
Totalmortality,N(%) 12(12.0%)
‡ Steroidusewastheindependentriskfactoraffectingpatientout- come,p<0.05,adjustedOR=0.14,CI:0.02,0.87.
∗ The distributions of smoking, pulmonary emphysema, tran- sientpopulationandbronchiectasisweresignificantlydifferent betweenmaleandfemalepatients,p<0.05.
100,000in2013.Asthelocalpopulationwascloseto71.8mil- lion,theannualincidenceofNTMinfectedpatientsandNTM pulmonarydiseasescouldbeestimated.In2011theywere3.07 and0.43per100,000,in2012were3.92and0.48per100,000,in 2013were3.36and0.17per100,000.Thedifferencesofannual incidencewerenotstatisticallysignificant(p>0.05).
Inconclusion,wefoundthattherewasahighpossibility thatNTMpulmonaryinfectedpatientmightbemisdiagnosed aspulmonarytuberculosisbyChinesepulmonarytuberculo- sisdiagnosticcriteria.Inaddition,agedmaleruralresidents, youngmalemanualtransientworkers,andagednon-smoking femalewerethreedistinctpatientgroups.Physiciansshould differentiate NTM pulmonary disease carefully from pul- monaryTB.
Funding
ThisstudywasfundedbytheNationalScientificandTechno- logicalMajorProjectofChina(GrantNos.2011ZX10004-901, 2013ZX10004-904, 2014ZX10004-008), and the Fundamental ResearchFundsfortheCentralUniversities.
Conflicts of interest
Theauthorsdeclarenoconflictsofinterest.
references
1.CassidyPM,HedbergK,SaulsonA,McNellyE,WinthropKL.
Nontuberculousmycobacterialdiseaseprevalenceandrisk factors:achangingepidemiology.ClinInfectDis.
2009;49:e124–9.
2.TechnicalGuidanceGroupoftheFifthNationalTB EpidemiologicalSurvey,TheOfficeoftheFifthNationalTB EpidemiologicalSurvey.Thefifthnationaltuberculosis epidemiologicalsurveyin2010.ChinJAntituberc.
2012;34:485–508.
3.XuK,BiS,JiZ,HuH,HuF,ZhengB,etal.Distinguishing nontuberculousMycobacteriafrommultidrug-resistant Mycobacteriumtuberculosis,China.EmergInfectDis.
2014;20:1060–2.
4.LiuJ,YueJ,YanZ,HanM,HanZ,JinL,etal.Performance assessmentoftheCapitalBiomycobacteriumidentification arraysystemforidentificationofmycobacteria.JClin Microbiol.2012;50:76–80.
5.GriffithDE,AksamitT,Brown-ElliottBA,CatanzaroA,DaleyC, GordinF,etal.AnofficialATS/IDSAstatement:diagnosis, treatment,andpreventionofnontuberculousmycobacterial diseases.AmJRespirCritCareMed.2007;175:367–416.
ShengBi1,Kai-jinXu1,Zhong-kangJi,Bei-wenZheng, Ji-fangSheng∗
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine,Hangzhou,China
∗Correspondingauthor.
E-mailaddress:[email protected](J.-f.Sheng).
1ShengBiandKai-jinXucontributedequallytothisarticle.
Received14July2015 Accepted8August2015
Availableonline9September2015 http://dx.doi.org/10.1016/j.bjid.2015.08.002
1413-8670/©2015ElsevierEditoraLtda.Allrightsreserved.
