Revised National Guidelines on
Management of
Tuberculosis in Children
National Tuberculosis Programme and
Senior Paediatricians, Myanmar
December 2016
Acknowledgements 5
Writing committee members for revised guideline 6
Abbreviations 7
Foreword 9
Preface 10
Introduction 12
Chapter 1 Diagnosis of TB in Children 15
2 StandardCaseDefinitionsofTBinChildren 23
3 ContactTracingandManagement 27
4 TreatmentofTBinChildren 33
5 SpecialSituationsinChildhoodTB 43
5.1 ManagementofDrug-ResistantTB(DR-TB)inChildren 43
5.2 ManagementofTBMeningitisandMiliaryTB 45
5.3 TBandHIVCo-infection 46
6 RecordingandReporting 53
7 RolesandResponsibilities 55
Annexes
Annex1.Proceduresforobtainingclinicalsamplesforsmearmicroscopyand
gastric aspiration procedures 59
Annex2.Administering,readingandinterpretingatuberculinskintest 63
Annex3.WeightChart 66
Annex4.RecordingandReporting Forms 68
References 70
CONTENTS
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ACKNOWLEDGEMENTS
WewouldliketoacknowledgetheMinistryofHealthandSports,Myanmarfortheoutstandingcommitment and leadership in developing this revisedNationalGuideline onManagement ofTBinChildren;WorldHealthOrganizationfortechnicalassistanceandtheGlobalFundtoFightAIDS,TuberculosisandMalariaforsupportingtheinitialdevelopmentanddisseminationprocessoftheNationalGuidelines.Furtherrevisionofthisguidelinetoincludenewlyavailabletreatmentand diagnostics was undertaken in 2016 with support from USAID Challenge TB.
Acknowledgements
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Writing committee members for revised guidelines
1) Director,DiseaseControl,DepartmentofPublicHealth
2) ProfessorTinMaungCho,RetiredProfessor/HeadofDepartmentofRespiratoryMedicine,YangonGeneralHospital
3) Professor/HeadofDepartmentofRespiratoryMedicine, (500)beddedSpecialistHospital,Yangon
4) Professor/Head of Department of Respiratory Medicine, Thingangyun Sanpya GeneralHospital,Yangon
5) Professor/Head of Department of Respiratory Medicine, Mandalay General Hospital,Mandalay
6) Professor/Head,DepartmentofChildHealth,UniversityofMedicine1,Yangon.
7) Professor/Head,DepartmentofChildHealth,UniversityofMedicine2,Yangon.
8) Professor/Head,DepartmentofChildHealth,UniversityofMedicine,Mandalay
9) Professor/Head,DepartmentofChildHealth,UniversityofMedicine,Magway
10)DeputyDirector(TB)/ProgrammeManagerofNationalTuberculosisProgrammeofMyanmar.
11)MedicalOfficer,TBUnit,WHOCountryOfficeforMyanmar
12)NationalConsultant,TBUnit,WHOCountryOfficeforMyanmar
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ABC AbacavirAFB Acid-FastBacilliAIDS AcquiredImmuneDeficiencySyndromeART Anti-RetroviralTherapyARV Anti-retroviraldrugAZT ZidovudineBAL Broncho-alveolarLavageBCG BacillusCalmette-GuéerinCD4 Sub-groupofT-LymphocytescarryingCD4antigensCT ComputerizedTomographyCPT CotrimoxazolePreventiveTherapyCTX CotrimoxazoleCXR ChestX-Rayd4T StavudineDOTS DirectlyObservedTreatment,ShortCourseStrategyDOT DirectlyObservedTreatmentDPT Diphtheria Pertusis TetanusDR-TB DrugResistantTuberculosisDST DrugSusceptibilityTestingE EthambutolEFV EfavirenzEPI ExpandedProgrammeonImmunizationEPTB ExtrapulmonaryTuberculosisFBC Full Blood CountFDC Fixed-dosecombinationFNA FineNeedleAspirationH IsoniazidHBV HepatitisBVirusHIV HumanImmunodeficiencyVirusIGRAs InterferonGammaReleaseAssayTestsIPT IsoniazidPreventiveTherapyIRIS ImmuneReconstitutionInflammatorySyndromekg KilogramLP Lumbar PunctureLpv/r Lopinavir/ritonavirMDR-TB Multidrug-resistanttuberculosis
ABBREVIATIONS
Abbreviations
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mg Milligrammm millimeterMRI MagneticresonanceimagingMOHS MinistryofHealthandSportsNAP NationalAIDSProgrammeNTP NationalTuberculosisProgrammeNTRL NationalTuberculosisReferenceLaboratoryNVP NevirapineMRI MagneticresonanceimagingNRTI NucleosideReverseTranscriptaseInhibitorNNRTI Non-NucleosideReverseTranscriptaseInhibitorOI OpportunisticInfectionOPV OralPolioVaccinePC PrimaryComplexPCR PolymeraseChainReactionPI Protease inhibitorPTB PulmonaryTuberculosisPPD PurifiedProteinDerivativeR RelapseR RifampicinRTV RitonavirSCC ShortCourseChemotherapySMX SulfamethoxazoleTAD Treatment after DefaultTAF Treatment after FailureTB TuberculosisTBM TuberculousMeningitisTI Transfer InTLC TotalLymphocyteCountTMP TrimethoprimTST Tuberculin Skin TestTU Tuberculin UnitUnion International Union Against Tuberculosis and Lung DiseaseUS UltrasoundWHO WorldHealthOrganizationWRD WHO-approvedrapiddiagnosticsZ PyrazinamideZDV Zidovudine3TC Lamivudine
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Tuberculosis(TB)isapreventableandcurabledisease,but1millionchildrensufferfromTBand210,000 children die of the disease worldwide in 2015.
TBisamajorchallengetopublichealthinMyanmar.Itis,inasense,aubiquitousdisease,affectingallsectionsofthesocietyandallagegroups.Itis,therefore,importanttoensureequitableaccessto care of international standards for all children with TB.
TB in children is oftenmissedor overlookeddue tonon-specific symptomsanddifficulties indiagnosis. Moreover, insufficient knowledge on childhood TB coupled with inappropriate andincorrect treatment is leading to theemergenceofmultidrug-resistant tuberculosis (MDR-TB).PracticalguidelinestothemedicalprofessioningeneralandNationalTuberculosisProgramme(NTP)inparticular,areneededforeffectivemanagementofchildhoodTB.Itwillserveasatoolfor setting national standards in the management of childhood TB, and it will also provide medical schools and clinicians working in both public and private sectors as a reference book.
Thisguidelinewasfirstdevelopedin2007butfurtherupdatedin2012and2016toensuretheuseofthelatestevidence-basedinternationalrecommendationsonchildhoodTB.TheguidelineswillfillthegapsinasystematicapproachtoTBinchildrenandwillhelptoachieveaninternationallyrecommendedstandardofcareatalllevelsofthehealthsysteminMyanmar.
National TB Programme
Department of Public Health
Ministry of Health and Sports
FOREWORD
Foreword
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Despite the world-wide effort, for decades, to control tuberculosis its incidence, prevalenceandimpactonglobalhealthisstillhighinmanypartsoftheworld.Theglobalcampaignonceemphasized and targeted upon infectious pulmonary tuberculosis (PTB). TheWHOStop TBstrategynowrecognizestheinadequacyofthatrationaleandseestheneedtocoverallformsof tuberculosis and ensures access to care of international standard in all parts of the world. The StopTBstrategythusexplicitlyaimstocorrectthechronicinadequacyofcareofTBinaparticularagegroupwhereinfectiousnessisrelativelylowbuttheimpactonglobalhealthhigh.TuberculosisinchildrenisnowpartoftheresponsibilityofNationalTuberculosisProgrammes(NTP).
AlthoughcurrentNTPguidelinescontainsomeguidancefortuberculosisinchildrenthedetailsof the strategy andactions are lacking. Furthermore, theworld-wide rise of incidence ofHIVinfection has had a great impact on tuberculosis both in adults and children. The need for a specificstrategyandactiononTB/HIVco-infectionisunarguablyevident.
To attend such needs, fill gaps in the currentNTPguidelines and complementNTP strategyandactions,aworkshopontuberculosisinchildrenwasorganizedbyMOHandWHOinMarch2007 in Yangon. The aim of the workshop was to review the situation of childhood tuberculosis (including management) in Myanmar and develop comprehensive guidelines which wouldencompass all aspects of management, control and prevention. Participants included leading senior paediatricians, responsible personnel from NTP and resident WHO TB coordinators.International expert help was also sought.
The workshop centred upon discussions on important aspects of management of childhood tuberculosis and producing consensus opinions. It elucidated pivotal areas to be covered, sought focalpersonsandsetthemotionfordevelopmentofproperguidelinesforMyanmar.
Awritingcommitteewasestablished.Thedraftscompiledbyfocalpersonswerereviewedandrevised several times.
A number ofWHO recommendations were incorporated into the guidelines. It covers all theessential areas about tuberculosis in children. The diagnosis of childhood tuberculosis is described inasystematicapproachsothatitwouldnotbetoocomplicatedforanylevelofcare.Theproblemofover-andunderdiagnosis issupposedtobeminimized.Treatment isalsostandardizedsothatinconsistenciesarelargelyavoided.RecordingandreportingofchildhoodTBispartofNTProutineactivities.Cohortanalysesofthesedatashouldprovideusrealisticfactsusefulforfurtherimprovement in treatment and control.
In 2010,WHOpublished “Rapid advice: treatment of tuberculosis in children”which includedreviseddosagesofanti-TBdrugsforuseinchildrenandtheregimensthatshouldbeusedfor
PREFACE
Preface
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different manifestations of the disease in children. In December 2011, a workshop was held in NayPyiTawandtheMinistryofHealthofMyanmaradaptedthenewWHOguidanceandthesechanges triggered the revision of the 2007MyanmarNationalGuidelines onManagement ofTuberculosisinChildren.Moreover,in2011,WHOdevelopedguidelinesforintensifiedtuberculosiscase-findingandisoniazidpreventivetherapyforpeoplelivingwithHIVinresource-constrainedsettings. These guidelines included a chapter of screening and prevention of TB in children living withHIVandtherecommendationshavebeentakenintoconsiderationintheserevisedchildhoodTBguidelines forMyanmar. In2014,WHOpublishedasecondeditionofguidelines forTB inchildrenwhichincludednewguidelinesfortheuseofXpertMTB/RIFinchildrenandin2016,newfixed-dosecombinations for thefirst-line treatmentofTB inyoungchildrenbecameavailable,leadingtoanupdateoftheMyanmarchildTBguidelinesfollowingconsultationwithstakeholdersbytheNTPin2016.
Thisrevisedguidelineisintendedtoserveasauser-friendlyreferenceforeverylevelofhealth-care providers involved in the care of children with tuberculosis.
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Tuberculosis isoneof themajorhealthproblems inMyanmar. It is therefore includedasoneof the three top priority diseases in theNational Health Plan.Around 140,000TB cases areregisteredandtreatedyearly.In2015,therewere42,608notifiednewbacteriologicallyconfirmedcases.Thetotalnumberofregisteredcasesincreasedfrom128,739in2008to147,984in2012.In2015,therewereatotalof139,854casesregistered.
TheincidenceofTBinchildren(<15yearsofage)ishighinMyanmar.DatafromtheNationalTuberculosisProgramme(NTP),MyanmarshowsthatchildhoodTBaccountedforonly3%ofthetotalcaseloadin2003,graduallyincreasingfrom21%in2007upto29%(42,434childTBcases)oftotalcaseloadin2012,andthenfallingto25%(or36,301cases)in2015.ForcasefindingofTBMeningitis,NTPdetected255casesin2007,increasingto848casesin2010,andfallingto246casesofTBMeningitisinchildrenin2015.
Thisalarmingsituationiscompoundedbytheriseofmultidrugresistant(MDR)TBinadultsandthescourgeofHIV-AIDSthroughouttheworld,especiallyinthedevelopingcountries.TheHIVsero-prevalenceamongTBpatientsinMyanmarisaround10%(NTPMyanmar,2011).MDR-TBamongnewsmearpositivecasesis4.2%and10.0%amongpreviouslytreatedcases(2007-2008countrywidesurvey,NTPMyanmar).
The management of childhood TB should be an important part of National TuberculosisProgramme because children with TB are sentinels for recent transmission from infectious adults inthecommunity.Childreninfectedundertheageof5yearsareathigherriskofdisseminateddiseasecarryinggreatermorbidityandmortality.Infectedchildrenconstituteareservoirforfutureinfection.
Thepost-2015EndTBstrategyoftheWorldHealthOrganization(WHO)buildsontheDirectlyObserved Treatment, Short Course Strategy (DOTS) initially developed by The Union andexpandedbytheWHOStopTBStrategyin2006,andhasacriticalroleinreducingtheworldwideburden of disease and thus protecting children from infection and disease. The management of childrenwithTBshouldbeinlinewiththeEndTBstrategy,takingintoconsiderationtheparticularepidemiologyandclinicalpresentationofTBinchildren.
Shortcoursechemotherapy(SCC)wasintroducedinMyanmarin1994whiletheDOTSstrategywas initiated in 1997. The treatment policy for childhood TB of NTP originally followed theadult intermittent regimebut thiswas replacedwithadaily treatment regimeon theadviceofpaediatriciansin2003.
Since then, thenumberof registeredcasesofsmearnegativepulmonaryTB,extrapulmonaryTBandprimarycomplexregisteredinNTPhasincreasedyearly.Thereisasignificantdegreeof
INTRODUCTION
Introduction
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over-diagnosisandunnecessarytreatmentforprimarycomplexdisease.Thismustbeavoidedsinceitentailsunnecessarydisadvantageandburdentothechildaswellasawasteofhealthcare resources.
Thisguidelinewasinitiallypreparedin2007byapanelofpaediatriciansandexpertsfromNTP,Myanmar,toaddressTBinchildren.ItprovidedrecommendationsbasedonthebestavailableevidenceandreflectedtheconsensusoftheMyanmarChildhoodTBWorkingGroup.In2011,theNTPadoptedWHO’srevisedguidelinesonthedosagesofanti-TBdrugsforuseinchildrenandtheregimensthatshouldbeusedfordifferentmanifestationsofthediseaseinchildren.Moreover,newrecommendationsonscreeningandpreventionofTBinchildrenlivingwithHIVwereagreedupon.Inaddition,algorithmsfordiagnosisofTBwithXpertMTB/RIFweredevelopedbytheNTPand are incorporated into these new guidelines.
The guidance presented here is an update to the 2007 guidelines and is designed to provide a standardizedapproachtothemanagementofchildhoodTBinthecontextoftheMyanmarsituation.Iiistailor-madeforcurrentpractice.In2011,NTPreviewedandrevisedthecurrentguidelineandincludedtherapidadvicesofWHO(2010)whichareappropriate forMyanmarcontext.Anewfixed-dosecombination(FDC)thatsimplifiesthetreatmentofyoungchildrenwithfirst-linetherapyusing the revised dosages was developed and became available in 2016. This has provided an opportunity toupdatetheguidelines, includingwithrecentdevelopmentsandfeedbackfromanationalworkshopattendedbyNTPandpaediatricians inFebruary2016.Expectedoutcomesof the use of guidelines are correct diagnosis, effective treatment and reduction of childhood TB.
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The diagnosis of TB in children relies on careful and thorough assessment of all the evidence derived from a careful history, clinical examination and relevant investigations.Most childrenwithTBhavepulmonaryTB.AlthoughbacteriologicalconfirmationofTBisnotalwaysfeasible,itshouldbesoughtwheneverpossiblebysputummicroscopy,cultureorbyusingXpertMTB/RIFforchildrenwithpresumptivepulmonaryTBwhoareoldenoughtoproduceasputumsample.Atrialoftreatmentwithanti-TBmedicationsisnotrecommendedasamethodtodiagnoseTBinchildren.Thedecisiontotreatachildshouldbecarefullyconsideredandoncesuchadecisionismade,thechildshouldbetreatedwithafullcourseoftherapy.
Risk Factors for Developing Childhood Tuberculosis
Presence of one or more of the following risk factors favours a diagnosis of TB in a child with suggestive clinical presentation.
• Closecontact (household,close relatives,caregiver,neighbourand teacher)withanewlydiagnosedsmear-positivecaseaswellassmear-negativebutculture-positivecase
• Age<5yearsofage• HIVinfection• Severe malnutrition, measles and immunosuppressive drugs or illnesses• AbsenceofBCGvaccination• Failuretothriveorweightloss(documented)
CHAPTER 1DIAGNOSIS OF TB IN CHILDREN
CHAP
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Chapter1:DiagnosisofTBinChildren
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Criteria for suspecting TB in Children
ThechildcanbeconsideredasapresumptiveTBcaseif2outof3followingfeaturesarepresent.
CLINICAL FEATURESSymptoms suggestive of childhood TB include:
• Cough Cough formore than2weekswhich isnot improvingwith fullcourseofantibioticsand/or
bronchodilators• Fever(38ºC) Feverformorethan2weeksafterexclusionofcommoncausesoffever(e.g.malaria)• Failuretogainweight(Weightlossifknown) See weight chart• Unexplainedlossofappetiteorlethargy
General Approach to diagnosis of TB in children
TREAT FOR TB
Suggestive symptoms (see text) with or without risk factors
Clinical assessment, including consider HIV test
Suspected Extrapulmonary TBSuspected Pulmonary TB
Enlargedglands
Other EPTB – see text for further investigation
Sputum positive Sputum negative or unavailable Fine needle aspiration or biopsy ifavailable
NegativeRequest CXR Positive
CXR typical or highlysuggestive
CXR normal oruncertain
Follow up and reassess, consider referral
Request sputum by expectoration (usually ≥ 8 years) or gastric aspirate for smear or Xpert MTB/RIF if available
• persistentsymptoms:coughformorethan2weeksand/orfever(≥38ºC)formorethan2weeks(unexplained)
• failuretogainweightorweightloss(consultweightchart)• history of contact with presumptive or diagnosed TB patient
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Signs suggestive of childhood TB are:
• Pulmonarytuberculosis
Signs of persistent pneumonia (cough or difficulty breathing with fast breathing or chestindrawing)afterfullcourseofappropriateantibiotics
• Extrapulmonarytuberculosis
1. Highlysuggestive
1.1. Pleural effusion
1.2. Acute vertebral gibbus
1.3. Non-painfulglandswithfistulaformationand/ordrainingsinus
2. Suggestive
2.1. Meningitisnotrespondingtoadequateantibiotics
2.2. Pericardial effusion
2.3. Swollennon-painfuljoints
2.4. Significantenlarged lymphglandsmore than2cmindiameterandmore than2 innumberwithoutfistulaformationbutwithnoknownlocalcauseandnotrespondingtousual antibiotics.
2.5. Distended abdomen with Ascites
2.6. ClinicalfeaturesindicativeofTuberculinhypersensitivity
(e.g.ErythemaNodosum,PhlyctenularConjunctivitis)
BACTERIOLOGICAL CONFIRMATIONA definitive diagnosis of TB can be achieved only by the demonstration of presence ofmycobacteriumbacillusinthelesionoritsproduct.ThemainlaboratorymethodsusedtodetectMycobacterium tuberculosis in a sample from a child suspected of having TB are smear for acid-fastbacilli,XpertMTB/RIFassay(usingreal-timePCR)ormycobacterialculture.However,inyoungchildren(<5years)whereTB ismainlypauci-bacillary, thisconfirmationmaynotbepossible inmanycases.Nevertheless,bacteriologicalconfirmation isdesirableandshouldbetriedinallcases.Notethatolderchildrenandadolescentsusuallycanandshouldprovidesputumbyexpectoration,andbacteriologicalconfirmationismorelikelythaninyoungchildren,especiallyasadolescentshaveasimilarformofpulmonaryTBasadults.
Sputum is obtained (by expectoration, gastric aspiration or sputum induction) to diagnosepulmonaryTB.Sputumsmearmicroscopyshouldbeusedforallchildrencapableofproducingsputum.Asmuchaspossible,cultureandXpertMTB/RIFshouldbeused forsmear-negative
Chapter1:DiagnosisofTBinChildren
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CHAP
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specimens.TheXpertMTB/RIFassayismoresensitivethansmearmicroscopy–abouttwotothreetimesmoresensitiveinchildren–butlesssensitivethanculture.TheotheradvantageofXpertMTB/RIF is that itdetermineswhether theM. tb is rifampicin-resistant.Therefore,XpertMTB/RIF(andcultureifavailable)isrecommendedinallchildrenthataresuspectedofhavingMDR-TB.
Sputum examination
• Sputumexaminationisessentialinolderchildren(≥8yearsofage)orinanyyoungerchildwhoisabletoprovideagoodqualitysputum
• Sputummustbecollectedafterinstructiononhowtocollectagoodspecimen(refertoAnnex1A)
• Atleast2sputumsamplesshouldbecollectedincludingoneearlymorningsample
• Sputum should be collected at all levels of the programme or care
• Sputum induction or gastric lavage on at least two specimens for bacteriological examination isencouragedintertiarycareinstitutions
Recommendations for gastric aspiration or lavage for TB diagnosis
• GastricaspirationorlavageisindicatedinchildrenwithpresumptiveTBunabletoproducesputum
• Gastricaspirationorlavageshouldbecarriedoutafter4hoursofnoteatingordrinking(fasting)
• Gastricaspirationorlavageshouldbeperformedaccordingtoprotocol(Annex1B)
• Gastricaspirationorlavageshouldbeavailableatalldistrictgeneralhospitals
• Thediagnosticyieldissimilartothatfromsputuminduction
• Thediagnosticyieldishigherfromatleasttwospecimensratherthanone
RADIOLOGICAL FEATURESCriteria for the diagnosis of TB on the chest radiograph
Although no specific radiological signs exist for a diagnosis ofTB, the following features arestronglysuggestiveinthediagnosisofTBwhenconsideredtogetherwithclinicalfeaturesandepidemiological context.
• UnequivocalhilarlymphglandenlargementwithorwithoutparenchymalopacificationMiliarymottling
• Largepleuraleffusion(≥1/3ofpleuralcavity)inchildrenusuallyolderthan5yearsofage
• Apicalopacificationwithcavitation(adult typedisease: rare inyoungchildren,common inadolescents)
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Note that hilar lymph node enlargement should be obvious and “unequivocal” to support thediagnosis. Misinterpretation of this finding is themajor reason for over-diagnosis of “primarycomplexdisease”.Ontheotherhand,chestradiographyisnotfullysensitiveinthatachildwithTBcanhavewhatappearstobeanormalchestradiograph.Therefore,thefindingsshouldalwaysbe interpreted in the context of clinical features.
IMMUNOLOGICAL EVIDENCE OF INFECTIONTuberculinSkinTests(TST)
Tuberculin skin tests areuseful in thediagnosis ofTB infection in young children for contacttracing. It is also useful as an adjunct test where the diagnosis of TB is uncertain, such as when there is no known contact in young children.TB cannot be ruled out in children based on anegativeTSTresult(refertoAnnex2).
Recommendations:
• TSTshouldbeavailableinRegionalandStateGeneralHospitals.
• ThevalueofTSTintheMyanmarcontextneedstobeevaluatedfurther.
• TST should be regarded as positive if induration is equal to or larger than 10 mm irrespective ofwhetherBCGhasbeenadministered.
• InHIVinfectedchildrenorchildrenwithseveremalnutrition,indurationof5mmorlargeristaken as positive.
TB/HIV CO-INFECTIONRecommendations for HIV testing
HIVtestingisnottobeofferedtoallchildrendiagnosedwithTB.Thefollowingchildrenshouldbetestedaftercounselling:
• MiliaryTB
• Severe acute malnutrition
• ClinicalsignssuggestiveofHIVdisease
• MotherknowntobeHIVpositiveoreitherparentsuspectedofbeingHIVinfected
• Relapseortreatmentfailure
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CHAP
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TESTS THAT ARE NOT RECOMMENDEDCommercial serological test to diagnose TB are inaccurate and should not be used.
InterferonGammareleaseassaytests(IGRAs)arenotdiagnosticforactiveTBandapositivetestindicatesinfection(asforTST).TheydonothaveclearadvantagesoverTSTinyoungchildren,areexpensiveandtechnicallychallengingrequiringsophisticatedlaboratorysupport.Therefore,IGRAsarenotrecommendedbyWHOforuseinlowandmiddleincomecountries.
Further information is required for the following tests before any recommendation can be made.
• XpertMTB/RIFonsomeextra-pulmonaryspecimenssuchaspleural,pericardialorperitonealfluid(lymphnodeaspirateifMDR-TBissuspected)
• Othernucleicacidamplificationtests(PCRtests)
SCORE CHARTS FOR THE DIAGNOSIS OF CHILDHOOD TBRecommendation:
AsthepublishedscorechartshaveunspecifiedsensitivitiesandspecificitiesandhavebeenshowntohaveapoorspecificityinHIVinfectedchildrentheyarenotrecommendedinthediagnosisofTB in children. The criteria of TB suspects provided in this guidelines is simple enough to be usefulforeverylevelofhealthcaresettingincludingbasic-healthstaffwhocoulduseitasanentrypoint for referral or further investigations.
DIAGNOSIS OF EXTRAPULMONARY TUBERCULOSISDiagnosis of extrapulmonary tuberculosis depends largely on site of the disease. Commonsites and recommended tests are mentioned below. For extrapulmonary TB,Mycobacterium tuberculosis can be detected in samples by smear or XpertMTB/RIF but the likely yieldwilldependonthesite.Forexample,bacteriologicalconfirmationiscommonforlymphnodeTB,notuncommonforTBmeningitis,butrareforpleural,pericardialorperitonealTB.AsforpulmonaryTB,ifachildissuspectedofhavingextrapulmonaryTBduetoMDR-TB,thensamplesshouldbeobtainedforXpertMTB/RIFandculture(ifavailable).
Diagnostic criteria for TB pleural effusion
• Largepleuraleffusion(≥1/3ofpleuralcavity)inchildrenolderthan5yearsofage
• Pleuraltapindicatesalymphocyterichexudate
• Clinical picture suggestive of TB
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Diagnostic tests for other Extrapulmonary TB
Disease Special investigations
Cervical/otherlymphglands Biopsy/Fineneedleaspiration(FNA)
TBMeningitis lumbarpuncture(LP),ComputerizedTomography(CT)ofbrain.
TBArthritis Aspiration,biopsy
TBAbdomen/ascites Ultrasound(US),AnalysisofAspiration
TBVertebra VertebralX-ray;CT/MRIofvertebralcolumn
RECOMMENDATIONS ON AVAILABILITY OF INVESTIGATIONS AT DIFFERENT LEVELS OF HEALTH CARETests that should be available in District General Hospital
• Lumbar puncture
• Aspiration of pleural effusion
• Fine needle aspiration of enlarged glands
• Lymphnodebiopsy
Tests that should be available in State / Regional Hospitals
• Ultrasound of the abdomen
• Fine needle aspiration of enlarged glands
• Lymphnodebiopsy
Tests that should be limited to tertiary care institutions:
ThesetestsarerequiredinthemanagementofseverecomplicatedTB:
• Computedtomographyofthechest,abdomen,brainandspine;MRI
• Bronchoscopy
• CultureandDrugSusceptibilityTest(DST)availableattheNationalTBReferenceLaboratory(NTRL)inYangonandtheUpperMyanmarTBReferenceLaboratoryinMandalay,especiallyinchildrenwithpresumptiveMDR-TB
• Otherinvasiveprocedures(e.g.mediastinallymphnodebiopsy,mediastinoscopy,thoracoscopyetc.)
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Symptoms suggestive of TB
Suspected pulmonary TB
Sputum for smear and Xpert MTB/RIF
Typical lymphnode TB Other EPTB
Sputum negative or not available
Chest radiograph
Normal/Uncertain
No risk factors
Follow up in 1 month
Sputum smear or Xpert positive
Highly suggestive TB
Risk factors
Refer for further investigation
(e.g. gastric lavage)
Refer toappropriate center
for furtherinvestigations
Suspected extrapulmonary TB
TREAT TB
ThefollowingflowchartshowsuggestedalgorithminassessmentofachildwithpresumptiveTBin township and district hospitals.
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Presumptive TB:ApatientwhopresentswithsymptomsorsignssuggestiveofTB(previouslyknownasTBsuspect).
A. CaseDefinitions• A bacteriologicallyconfirmedTBcase is one from whom a biological specimen is positive
bysmearmicroscopy,cultureorWRD(suchasXpertMTB/RIF).Allsuchcasesshouldbenotified,regardlessofwhetherTBtreatmenthasstarted.
• A clinically diagnosed TB case is onewhodoesnot fulfil the criteria for bacteriologicalconfirmationbuthasbeendiagnosedwithactiveTBbyaclinicianorothermedicalpractitionerwhohaddecidedtogivethepatientafullcourseofTBtreatment.ThisdefinitionincludescasesdiagnosedonthebasisofX-rayabnormalitiesorsuggestivehistologyandextrapulmonarycases without laboratory confirmation. Clinically diagnosed cases subsequently found tobe bacteriologically positive (before or after starting treatment) should be reclassified asbacteriologicallyconfirmed.
BacteriologicallyconfirmedorclinicallydiagnosedcasesofTBarealsoclassifiedaccordingto:
- Anatomicalsiteofdisease;
- Historyofprevioustreatment;
- Drugresistance;
- HIVstatus.
A.1Classificationbasedonanatomicalsiteofdisease
Pulmonarytuberculosis(PTB)referstoanybacteriologicallyconfirmedorclinicallydiagnosedcaseofTBinvolvingthelungparenchymaorthetracheobronchialtree.MiliaryTBisclassifiedas PTB because there are lesions in the lungs. Tuberculous intrathoracic lymphadenopathy(mediastinaland/orhilar)ortuberculouspleuraleffusion,withoutradiographicabnormalitiesinthelungs,constitutesacaseofextrapulmonaryTB.ApatientwithbothpulmonaryandextrapulmonaryTBshouldbeclassifiedasacaseofPTB.
Extrapulmonary tuberculosis (EPTB) refers to any bacteriologically confirmed or clinicallydiagnosedcaseofTBinvolvingorgansotherthanthelungs,e.g.pleura,lymphnodes,abdomen,genitourinarytract,skin,jointsandbones,meninges.
CHAPTER 2STANDARD CASE DEFINITIONS OF TB IN CHILDREN
Chapter2:StandaradCaseDefinitionsofTBinChildren
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A.2ClassificationbasedonhistoryofpreviousTBtreatment(patientregistrationgroup)
New:PatientshaveneverbeentreatedforTBorhavetakenanti-TBdrugsforlessthan1month.
Previously treated:Patientsreceived1monthormoreofanti-TBdrugsinthepast.Theyarefurtherclassifiedbytheoutcomeoftheirmostrecentcourseoftreatmentasfollows:
Relapse: Patients have previously been treated for TB, were declared cured or treatmentcompleted at the end of their most recent course of treatment, and are now diagnosed with a recurrentepisodeofTB(eitheratruerelapseoranewepisodeofTBcausedbyreinfection).
Treatment after failure:PatientsarethosewhohavepreviouslybeentreatedforTBandwhosetreatment failed at the end of their most recent course of treatment.
Treatment after loss to follow up: Patients have previously been treated for TB and weredeclared lost to follow-up at the end of their most recent course of treatment. (These werepreviouslyknownastreatmentafterdefaultpatients.)
Other previously treated:PatientsarethosewhohavepreviouslybeentreatedforTBbutwhoseoutcome after their most recent course of treatment is unknown or undocumented.
Previous treatment history unknown:Patientswithdonotfitintoanyofthecategorieslistedabove.
A.3ClassificationbasedonHIVstatus
HIV positiveTBpatient refers toanybacteriologically confirmedor clinically diagnosedcaseofTBwhohasapositiveresultfromHIVtestingconductedatthetimeofTBdiagnosisorotherdocumentedevidenceofenrolmentinHIVcare,suchasenrolmentinthepre-ARTregisterorintheARTregisteronceARThasbeenstarted.
HIV negativeTBpatientreferstoanybacteriologicallyconfirmedorclinicallydiagnosedcaseofTBwhohasanegativeresultfromHIVtestingconductedatthetimeofTBdiagnosis.AnyHIVnegativeTBpatientsubsequentlyfoundtobereclassifiedaccordingly.
HIV status unknownTBpatientreferstoanybacteriologicallyconfirmedorclinicallydiagnosedcaseofTBwhohasnoresultofHIVtestingandnootherdocumentedevidenceofenrolmentinHIVcare.Ifthepatient’sHIVstatusissubsequentlydetermined,heorsheshouldbereclassifiedaccordingly.
A.4Classificationbasedondrugresistance
Casesareclassifiedincategoriesbasedondrugsusceptibilitytesting(DST)ofclinicalisolatesconfirmedtobeM. tuberculosis:
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SEVERE EPTB LESS SEVERE EPTB
• Meningitis • Lymphnode
• Miliary • Pleuraleffusion(unilateral)
• Pericarditis • Peripheral joint
• Bilateral or extensive pleural effusion • Adrenal gland
• Osteoarticular • Skin
• Intestinal
• Genitourinary
• Monoresistance:resistanceonefirstlineanti-TBdrugonly.
• Polydrug resistance: resistancetomorethanonefirst lineanti-TBdrug(other thanbothisoniazidandrifampicin).
• Multidrug resistance:resistancetoatleastbothisoniazidandrifampicin.
• Extensive drug resistance:resistancetoanyfluoroquinoloneandtoatleastoneofthreesecond-lineinjectabledrugs(capreomycin,kanamycinandamikacin),inadditiontomultidrugresistance.
• Rifampicin resistance: resistance to rifampicin detected using phenotypic or genotypicmethods, with or without resistance to other anti-TB drugs. It includes any resistance torifampicin,whethermonoresistance,multidrugresistance,polydrugresistanceorextensivedrug resistance.
Severityofdisease(PTB)InadditiontobacteriologicallyconfirmedpulmonaryTB,formsofclinicallydiagnosedpulmonaryTBthatfitthecriteriaofseverityfortheuseoffourdrugsintheintensivephaseincludethosewithextensiveparenchymalchanges,thosewithcavitiesonCXR,thosewhoalsohaveextrapulmonarydiseaseandthosewithHIVco-infection.
Severityofdisease(EPTB)Bacillaryload,extentofdiseaseandanatomicalsiteareconsiderationsindeterminingTBdiseaseseverity and the appropriate treatment. The involvement of some anatomical sites results inclassificationasseverediseaseifthereisasignificantacutethreattolife(e.g.pericardialTB),ariskofsubsequentseverehandicap(e.g.spinalTB),orboth(e.g.meningealTB)
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ContacttracingisavaluablemeansofidentifyingnewTBcasesanditisrecommendedbyWHOandTheUnion.Therefore,contacttracingisonecrucialcomponentofNTPactivitiesespeciallyincasefinding.
Youngchildrenlivinginclosecontactwithasourcecaseofsmear-positivepulmonaryTBareatparticular risk of TB infection and disease. The risk of infection is greatest if the contact is close and prolonged such as the contact an infant or toddler has with a mother or other caregivers in thehouseholdandespeciallysoiftheindexcaseisnottreated.Theriskofdevelopingdiseaseafter infection ismuchgreater for infantsandyoungchildrenunder5yearsofage,especiallyunder3years.
The main purposes of child contact screening are to
• Identifysymptomaticchildren(e.g.childrenofanyagewithundiagnosedTBdisease);
• Providepreventivetherapyforsusceptibleindividuals(e.g.asymptomaticchildrenof<5yearsofageinclosecontactwithasmear-positivepulmonaryTBcase)
DefinitionsSource case
AcaseofpulmonaryTB(usuallysputumsmearpositive)which results in infectionordiseaseamong contacts
Contacts for screening
Allclosecontactsofasourcecaseofanyage, includingyoungchildren<5years,shouldbescreenedforsymptomssuggestiveofTB.
Close contact
Livinginthesamehouseholdasasourcecaseorinfrequentcontactwithasourcecase(e.g.caregiver,grandparents,relatives)
Strategy for Contact TracingContacttracingshouldbereinforcedintwoways:
- Through indexadultcase(DetectionofTB inclosecontactsofusuallyadultsourcecase,particularlysputumsmearpositivecases)(downstreamtracing)
CHAPTER3CONTACT TRACING AND MANAGEMENT
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- ThroughclosecontactsofchildhoodTBcases(DetectionofsourcecaseforapaediatricTBpatient,alsoknownasreversecontacttracing)(upstreamtracing)
Parentsandcaregiversaretobestronglyencouragedtobringchildrenforcontactscreeningtohealthcentre(passivecontactscreening).Alternatively,ifthechildisfoundwithTBdisease,his/herfamilymembersandneighboursshouldalsoundergoTBscreening.
Approach to Contact screeningThree main steps used for contact screening
(a) clinicalscreening:symptomsassessmentofallcontactsofanyage,includingchildren
(b) clinical evaluation forTB: any contactwith symptomssuggestiveofTB should be furtherevaluatedforTB,e.g.sputum,ChestX-rayetc.
(c) contactsthatareyoungchildren(<5years)orHIV-infectedofanyage,andthatdonothaveactiveTBshouldbeofferedpreventivetherapy
IsoniazidPreventiveTherapy(IPT)PreviouslyinMyanmartherewasnoIPTpolicyasapreventivetreatmenttochildrenincontactwithaninfectiouscase.Childrenunder3yearsofagehavethehighestriskofdevelopingTBmeningitis and disseminated disease after infection. This Guideline, thus, adopt a policy toadministerIPTdailyfordurationof6months(Isoniazid10mg/kg)toasymptomaticchildrenof<5yearsofage,whoareinclosecontactwithasmearpositivecase(seefigurebelow).Fieldstudies(operationalresearch)hadshownthatasimplesymptomassessmentcanbeeffectivelyusedinthecommunityforcontactmanagementwhentuberculinskintest(TST)orchestX-rayisnotavailable.ForthechildwithanydegreeofuncertaintyaboutactiveTBdisease,IPTmustnotbestartedandthechildshouldbereferredtothenextlevelofcare(paediatricianorNTP)forfurther evaluation and management.
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ApproachtocontactmanagementwhenchestX-rayandtuberculintestarenotreadilyavailable
Child in close contact with source case of smear positive PTB
< 5 years of age
If becomes symptomatic
well
6 H
well
No treatment
symptomatic symptomatic
≥5 years of age
If becomes symptomatic
Adapted from Guidance for National Tuberculosis Programmes on the Management ofTuberculosis in Children,WHO 2006, adapted toMyanmar during the national workshop onChildhoodTB,YangonMarch2007
IPT RegimenRecommendeddosageis10(7-15range)mg/kgisoniaziddailyfor6months(6H).AnalternativepreventivetherapyregimenwhichisaseffectiveandsafeasIPTisdailyrifampicin/isoniazidfor3months(3RH)usingthenewFDC, likelytobemoreconvenientfornew-bornsbecauseit isdispersible.
Evaluate for TB
If positive, treat for TB. If not TB and<5 years, give preventive therapy
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Dosageofisoniazidbyweightbandsupto25kgusingeither50mgor100mgtablets.Once25kgormorethencanuse300mgtablet.
NTPhasdevelopedanIsoniazidPreventiveTherapyCardandRegisterforthesechildren(refertoAnnex4).
Special circumstancesContact tracing and HIV infected children
HIVinfectedchildrenhaveaveryhighriskofdevelopingprogressionofdiseaseonceinfectedwith Mycobacterium tuberculosis,theyoungerchildrenbeingatthehighestrisk.
PreventionhasbecomeanimportantstrategytoreducemortalityandmorbidityofTBinpeoplelivingwithHIV/AIDS.Isoniazidischeapandbactericidalagainstbothextracellularandintracellularbacilli. In latentTBinfection,thebacterialburdenissmallallowingmonotherapy.Therefore,topreventTB inHIV infectedchildren, it is recommended that they receive IsoniazidPreventiveTherapy (IPT). It is evenmore important to exclude activeTBdisease inTB/HIV co-infectedpatientswhichmightnotbesoeasy;and,therefore,patientsmaybereferredtothenextlevelofcare to exclude active TB disease before deciding to administer IPT. TB contact tracing should be carriedoutinHIVinfectedchildrenofallages.
(Ref:“GuidelinesforclinicalmanagementofHIVinfectioninchildreninMyanmar”(MOHNAP2011,3rdedition).
ChildrenlivingwithHIVwhoaremorethan12monthsofageandwhoareunlikelytohaveactiveTBonsymptom-basedscreening,andhavenocontactwithaTBcaseshouldreceive6monthsofIPTaspartofacomprehensivepackageofHIVpreventionandcareservices.
InchildrenlivingwithHIVwhoarelessthan12monthsofage,onlythosewhohavecontactwithaTBcaseandwhoareevaluatedforTB(usinginvestigations)shouldreceivesixmonthsofIPTif the evaluation shows no TB.
Weight bands Isoniazid alone or IPT Alternative regimen using RH 75/50
2-3.9kg 25 mg 1/2
4-7.9kg 50 mg 1
8-11.9kg 100 mg 2
12-15.9kg 150 mg 3
16-24.9kg 200 mg 4
25 kg + 300mg
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Child contact with an MDR-TB source case
Therearenoevidence-basedrecommendationsavailableonthepreventionofMDR-TBinchildrenafterexposure.Childrenexposed toaMDR-TBcaseare therefore tobe followedupevery3monthsforfirstyearandeverysixmonthsforsecondyear.IfthechildrenbecomesymptomaticandhavetheclinicalsignsorCXRchangeshighlysuggestiveofTB,theyshouldbereferredtospecialMDR-TBtreatmentcentrefordiagnosis,treatmentandcare(thecentrethattreatsadultswithMDR-TBaswell).
Prevention of TB in a baby born to a mother with newly diagnosed TB
If themother isonanti-TBtreatment for2weeksor longer, there isnoneedtogive isoniazidprophylaxis.Examinethebabytoensurethatthebabyishealthy(excludecongenitalTB).GiveBCGvaccinationaccordingtothecurrentExpandedProgrammeonImmunization(EPI)schedule.
If themother isrecentlydiagnosedandnotreceivingtreatmentorreceivingtreatment for lessthan 2weeks, start the prophylaxis for the babywith isoniazid (10mg/kg) for 6months andfollow-upmonthlytoexcludeactivedisease.After6monthsifthechildishealthy,theprophylaxiscourseisfollowedbyBCGimmunization.Breastfeedingcanbesafelygivenduringthisperiodandthereisnoneedtoseparatebabyfrommother.Childrenwithactivediseaseshouldbegivenfulltreatmentandregisteredaccordingly.
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CHAPTER 4TREATMENT OF TB IN CHILDREN
Themainobjectivesofanti-TBtreatmentareto:
• CurethepatientwithTB(byrapidlyeliminatingmostofthebacilli);
• Prevent death from active TB or its late effects;
• PreventrelapseofTB(byeliminatingthedormantbacilli);
• Preventthedevelopmentofdrugresistance(byusingacombinationofdrugs);
• DecreaseTBtransmissiontoothers(smear-positivecases)
Recommended treatment regimensAnti-TBtreatmentisdividedintotwophases:anintensivephaseandacontinuationphase.Thepurposeoftheintensivephaseistorapidlyeliminatethemajorityoforganismsandtopreventtheemergence of drug resistance. This phase uses a greater number of drugs than the continuation phase. The purpose of the continuation phase is to eradicate the dormant organisms. Fewer drugsaregenerallyusedinthisphasebecausetheriskofacquiringdrugresistanceislow,asmostoftheorganismshavealreadybeeneliminated.Ineitherphase,treatmentistobegivendaily.Thetablebelowshowsthefirstline(oressential)anti-TBdrugsandtheirrecommendeddoses.
Recommendeddosesoffirstlineanti-TBdrug
Drug
Recommended daily dosing
Previous New
Dose and range (mg/kg)
Maximum(mg)
Dose and range (mg/kg)
Maximum(mg)
Isoniazid 5(4-6) 300 10(7-15) 300
Rifampicin 10(8-12) 600 15(10-20) 600
Pyrazinamide 25(20-30) - 35(30-40) -
Ethambutol 20(15-25) - 20(15-25) -
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Streptomycinisnolongerrecommendedasafirst-linedrugandhasverylimiteduseinchildren.EthambutolisrecommendedtobeusedinchildrenasthefourthdrugonlyinsevereformsofTBorinHIV-infectedchildrenregardlessofage.Themajorpotentialtoxicityfromethambutolisopticneuritisthatcanleadtoblindness,ariskthatrelatestothedosageanddurationused.However,theriskoftoxicityisnegligibleifcorrectdosagesareusedforjust2monthsofintensivephase.
TherecommendedtreatmentregimensforeachTBtreatmentcategoriesforchildren(seetablebelow)aregenerallythesameasforadults.NewcasesfallundercategoryI(newsmearpositivepulmonary TB; new smear negative pulmonary TB with extensive parenchymal involvement;severe forms of extrapulmonary TB; concomitant HIV disease) or category III (new smearnegativepulmonaryTB–otherthanincategoryI;lesssevereformsofextrapulmonaryTB).MostchildrenwithTBhaveuncomplicated (smearnegative)pulmonary/TBornon-severe formsofextrapulmonaryTB,andthereforefallunderdiagnosticcategoryIII.ChildrenwithbacteriologicallyconfirmedpulmonaryTB,extensivepulmonaryinvolvementorsevereformsofextrapulmonaryTB(e.g.abdominalorbone/jointTB)fallunderdiagnosticcategoryI,regardlessofageandweight.ChildrenwithTBmeningitisandmiliaryTBdeservespecialconsideration(refertoChapter5).ThepreviouscategoryII(orretreatmentregimen)isnolongerrecommended.
MostchildrenwithTBwillshowsignsofimprovementafter2to4weeksofanti-TBtreatment.Ifachildisfailingtorespondtoanti-TBtreatmentat1to2monthsafterstartingtreatment,considerpooradherence,incorrectdiagnosisorthepossibilityofMDR-TB.Ifthereispooradherenceandthechilddoesnot receiveanti-TB treatment formore than2weeks in the intensivephaseormorethan2monthsinthecontinuationphaseandbecomessymptomatic,thenrestartanti-TBtreatment.TreatmentfailureismorecommoninHIV-infectedchildren.ThisisbecausetheymayhaveotherHIV-relatedchroniclungdiseasenotduetoTB,orbecauseofimmunosuppression,andsoshouldbereceivinganti-retroviraltherapy(ART)inadditiontoanti-TBtherapy.
Recommended treatment regimens for children in each TB diagnostic categoryDirect observation of drug administration (DOT) is recommended during the initial phase oftreatmentandwheneverthecontinuationphasecontainsrifampicin.WHOrecommendedrapidadviceonTBtreatmentinchildrenwasadaptedinMyanmarinDecember2011withthefollowingexception:forchildrenbelow8yearsofage,thethreedrugregimenshouldbeusedi.e.excludingethambutol.However,ifHIVpositiveandorsevereformsofpulmonaryandextrapulmonaryTB,thefourdrugregimen(RHZE)shouldbeusedwithclosemonitoringofadverseeffects.
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Type ofTB Patient
TB cases
Regimen
Intensivephase
Continuation phase
• Children<8yearsofage(exceptions:seebelow)
2HRZ 4HR
Newcase
• Children≥8yearsofage• Children<8yearsofagewithsevereformsofpulmonary/extrapulmonaryTBorwhoareHIV-infected
2HRZE 4HR
• Meningitis/disseminatedTBdisease• OsteoarticularTB
2HRZE 10HR
Previouslytreated case
• Relapse• Treatment after failure• Treatmentafterlosstofollow-up
3HRZE 5HRE
MDR-TB
Speciallydesignedstandardizedorindividualizedregimens(refertoChapter5andMyanmarNationalguidelinesonManagementofMDR-TB)
H:isoniazid;R:rifampicin;E:ethambutol;Z:pyrazinamide
Aregimenconsistsoftwophases:theinitialandcontinuationphases.Thenumberatthefrontofeach phase represents the duration of that phase in months.
e.g.2HRZE/4HRthetotaldurationofinitialphaseis2monthsdailywithisoniazid(H),rifampicin(R),pyrazinamide(Z),andethambutol(E)for2monthsfollowedbyisoniazid(H)andrifampicin(R)for4months.
Re-treatment casesInchildhoodTBcaseswhenanti-TBtreatmentfailsorarelapseoccurs,everyeffortshouldbemadetofindthemostlikelycauseforthefailureorrelapse.Itisimportanttoestablishifthechildhasbeenadherenttotreatment.Mycobacterialcultureanddrugsusceptibilitytestingshouldbeperformed forall re-treatment caseswherepossibledue to thepossibilityof treatment failurebecause the childhasMDR-TB. IfMycobacterial cultureanddrugsusceptibility testing isnotpossibleortheresultissensitiveTB,retreatmentregimenisgiventothosechildren.HIVtestingshould be performed to all retreated childhood TB cases.
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CorticosteroidsCorticosteroidsmaybeused for themanagement of somecomplicated formsofTB, e.g.TBmeningitis, TB glands causing airway obstruction, and TB pericardial effusion. In cases ofadvanced TB meningitis, corticosteroids have been shown to improve survival and decrease morbidity,andthusareindicatedinallcasesofTBmeningitis.Thedrugrecommendedforuseisprednisolone,inadosageof2mg/kgdaily,isincreasedupto4mg/kgdailyinthecaseofthemostseriouslyillchildren,withamaximumdosageof60mg/dayfor4weeks(refertoChapter5).Thedoseshouldthenbegraduallyreduced(tapered)over2-4weeksbeforestopping.
Administering treatment and ensuring adherenceChildren, their parents and other family members, and other caregivers should be educatedabout TB and the importance of completing treatment. The support of the child's parents and immediatefamilyisvitaltoensureasatisfactorytreatmentoutcome.Oftenahealthcareworkercanobserveor administer treatment, but if this arrangement is not convenient for the family,a trainedcommunitymember (preferablysomeoneother than thechild’sparentor immediatefamily) can undertake this responsibility.All children should receive treatment free of charge,whetherthechildissmear-positiveatdiagnosisornot.Fixeddosecombinationsofdrugsshouldbeusedwheneverpossible to improvesimplicityandadherence.Patient treatmentcardsarerecommended for documenting treatment adherence.
Children with severe forms of TB should be hospitalized for intensive management wherepossible.Conditionsthatmerithospitalizationinclude:(i)TBmeningitisandmiliaryTB,preferablyfor at least the first 2months, (ii) respiratorydistress, (iii) spinalTB,and (iv) severeadverseevents,suchashepatotoxicity(e.g.jaundice).Ifitisnotpossibletoensuregoodadherenceandtreatmentoutcomeonanoutpatientbasis,somechildrenmayrequirehospitalizationforsocialor logistic reason.
Introduction of the “new” FDCsNewfixeddosecombinations(FDCs)forfirst-linetreatmentofTBinchildrenoflessthan25kgwereintroducedbyMyanmarNTPin2016.TheFDCfortheintensivephasecontainsRifampicin75mg;Isoniazid50mgandPyrazinamide150mg(RHZ:75/50/150),andforthecontinuationphaseisacombinationofRifampicin75mgandIsoniazid50mg(RH:75/50).Thepreparationisa dispersible tablet that dissolves in water and can be taken as a liquid which makes treatment easier for young children. The preparation also facilitates treatment with the correct, reviseddosages(WHO,2010)withouttheneedforadditionalpreparationsaspreviously.ThefollowingtableprovidesguidanceforuseofthenewFDCsinchildrenlessthan25kgbyweightbandstobeconsistentwiththerecommendeddosages.Olderchildrenandadolescentsthatweighmorethan
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Numbersoftabletsbyweightbandforyoung(<8years)childrenwithnon-severeformsof TB
Numbers of tablets by weight band for all children with severe forms of TB and all older (≥8yearsofage)childrenwithTB
Numbers of tablets
Intensive Phase Continuation Phase
RHZ RH
Weight bands 75/50/150 75/50
4-7.9kg 1 1
8-11.9kg 2 2
12-15.9kg 3 3
16-24.9kg 4 4
≥25kg Useadultdosagesandpreparations-seeabovetext
Numbers of tablets
Intensive Phase Continuation Phase
RHZ E RH
Weight bands 75/50/150 100 75/50
4-7.9kg 1 1 1
8-11.9kg 2 2 2
12-15.9kg 3 3 3
16-24.9kg 4 4 4
≥25kg Use adult dosages and preparations
25kgreceiveadultdosagesandpreparationsaccordingtoMyanmarnationalguidelines,i.e.if25-39.9kg,thentwoRHZE150/75/400/275inintensivephaseandtwoRH60/60incontinuationphase.
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Numbersoftabletsbyweightbandforyoung(<8years)childrenwithnon-severeformsof TB
Therearesome importantconsiderationsas theMyanmar transitions to theuseof the “new”FDC.It is importantthatsingledosepreparationsremainavailableofrifampicin, isoniazidandpyrazinamidesuitableforyoungchildrencontinuetobeavailableforthemanagementofadversereactionstoFDCs(althoughextremelyrare).Singledrugpreparationofisoniazidisparticularlyimportant in order to implement preventive therapy for children. It is also important to haveguidancefortheuseoftheolderFDCsofRHZ60/30/150andRH60/30untilthesepreparationsarefullyreplacedbythenewFDCs.
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Numbers of tablets
Intensive Phase Continuation Phase
RHZ RH
Weight bands 60/30/150 60/30
4-6.9kg 1 1
7-10.9kg 2 2
11-14.9kg 3 3
15-19.9kg 4 4
20-24.9kg 5 5
≥25kg Use adult dosages and preparations
Numbers of tablets by weight band for all children with severe forms of TB and all older (≥8yearsofage)childrenwithTB
Follow upIdeally,eachchildshouldbeassessedbytheNTP(ortheMedicalOfficerdesignatedbytheNTPtoprovidetreatment)atleastatthefollowingintervals:2weeksaftertreatmentinitiation,andattwo-,five-andsix-month.Whenthepatientlivesinremotearea,follow-upshouldbedoneatleastevery2months.Follow-upmayalsobecarriedoutbythePaediatricianfromDistrictorState/RegionalHospitalinchargeofthecase,orbyapaediatricianorgeneralpractitionerinprivatepracticeincollaborationwiththeNTP.
Theassessment should include, asaminimum; symptomassessment, assessmentof treatmentadherence,enquiryaboutanyadverseeventsandweightmeasurement.Medicationdosagesshouldbeadjustedtoaccountforanyweightgain.Adherenceshouldbeassessedbyreviewingthetreatmentcard,andpillcountorblisterpackcount.Afollow-upsputumsampleforsmearmicroscopyat2,5and6monthsaftertreatmentinitiationshouldbeobtainedforanychildwhowassmear-positiveatdiagnosis.
Followupchestradiographsarenotroutinelyrequiredinchildren,particularlyasmanychildrenwillhaveaslowradiologicalresponsetotreatment.CXRmayberepeatedincasesofextensivepulmonaryinvolvement,continuedsymptomsortreatmentfailureregardlessofsmearpositivity.Achildwhoisnotrespondingtoanti-TBtreatmentshouldbereferredforfurtherassessmentand
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Numbers of tablets
Intensive Phase Continuation Phase
RHZ E RH
Weight bands 60/30/150 100 mg 60/30
4-6.9kg 1 1 1
7-10.9kg 2 2 2
11-14.9kg 3 2 3
15-19.9kg 4 3 4
20-24.9kg 5 4 5
≥25kg Use adult dosages and preparations
management.Thesechildrenmayhavedrug-resistantTB,anunusualcomplicationofpulmonaryTB, other causes of lung disease or problems with treatment adherence.
The NTP is responsible for organizing continuation of treatment and ensuring the recording and reporting of cases and their outcomes. Good communication is necessary between the NTP and clinicians treating children with TB for successful outcomes and future cohort analysis.
Immune reconstitutionSometimes known as a paradoxical reaction, a temporary clinical deterioration (with new orworseningofsymptoms,signsorradiologicalmanifestations)sometimesoccursafterbeginninganti-TBtherapyduetorestorationofcapacitytomountaninflammatoryimmuneresponse.Thiscansimulateworseningdisease,withfeverandincreasedsizeoflymphnodesortuberculomas.Immunereconstitutioncanoccurwith improvednutritionalstatusoranti-TBtreatment itself. InTBpatientswhoareco-infectedwithHIV,clinicaldeteriorationduetoimmunereconstitutioncanoccurafter initiationofantiretroviral therapy(ART)andisknownasthe immunereconstitutioninflammatorysyndrome(IRIS).Inallcasesanti-TBtreatmentshouldbecontinued.Insomecases,theadditionofcorticosteroidsmightbeuseful.IfthechildisacutelyillfromtheIRIS,steroidsareindicated(prednisone1-2mg/kg/day).Ifthereisanydoubt,thechildshouldbereferredtothenext level of care.
Adverse eventsThetablebelowshowsasymptom-basedapproachtothemostcommonadverseeffectsoftheessentialanti-tuberculosisdrugs.Adverseeffectsareclassifiedasminorandmajor.Ingeneral,apatientwhodevelopsminoradverseeffectsshouldcontinuetheanti-TBtreatment.Thepatientalsoreceivessymptomatictreatment.Ifapatientdevelopsamajorside-effect,thetreatmentofthe offending drug is needed to be stopped. Further management depends on the nature of the adverse reaction. Patients with major adverse reactions should be referred to the hospital.
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Side - effectsDrug(s)probably
responsible
Management Level of Health Facility to Manage
MINOR Continue anti-TB drugs, check drug doses
PRIMARY CARE LEVEL
(ruralhealthcentre;urban health
centre)
Anorexia, nausea, abdominal pain
Pyrazinamide,rifampicin
Givedrugswithsmallmealor last thing at night
Joint pains pyrazinamide Aspirin
Burning sensation in the feet isoniazid Pyridoxine50-75mg
Orange/redurine rifampicin
Reassurance;patientsshould be told when starting treatment that this commonlyhappensandisnormal
MAJOR Stopresponsibledrug(s)
FIRST LEVEL OF CARE AND
ABOVE
(township,district,Region,State, teaching
hospital)
Itching, skin rash Isoniazid,rifampicin,pyrazinamide Stopanti-TBdrugs
Jaundice(othercausesexcluded),hepatitis
Isoniazid,pyrazinamide,rifampicin
Stopanti-TBdrugs
Confusion(suspectdrug-inducedacute live failure if jaundiceispresent)
Mostanti-TBdrugsStopanti-TBdrugs,urgentliver function tests and prothrombin time
Visualimpairment(othercausesexcluded)
ethambutol Stop ethambutol
Shock, purpura, acute renal failure rifampicin Stop rifampicin
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Adverseeventscausedbyanti-TBdrugsaremuchlesscommoninchildrenthaninadults.
Themostimportantadverseeventisthedevelopmentofhepatotoxicity,whichcanbecausedbyisoniazid,rifampicinorpyrazinamide.Serumliverenzymelevelsarenottobemonitoredroutinely,asasymptomaticmildelevationofserumliverenzymes(lessthanfivetimesthenormalvalues)isnotanindicationtostoptreatment.However,theoccurrenceoflivertenderness,hepatomegalyorjaundiceshouldleadtoinvestigation,measurementofofserumliverenzymelevelsandtheimmediatestoppingofallpotentiallyhepatotoxicdrugs.Patientsshouldbescreened forothercauses of hepatitis, and no attempt should be made to reintroduce these drugs until liver functions havenormalized.Anexpert (experienced inmanagingdrug-inducedhepatotoxicity)shouldbeinvolved in the further management of such cases. If treatment for TB needs to be continued for severe formsofTB,non-hepatotoxicanti-TBdrugsshouldbe introduced (e.g.ethambutoloranaminoglycoside).Iffluoroquinoloneistobeusedinthelatter,thisshouldonlybedoneuponconsultationwithanddecisionbyaHospitalexpertcommitteeandwelldocumented.
Pyridoxine supplementationIsoniazid may cause symptomatic pyridoxine deficiency, particularly in severelymalnourished children and HIV-infected children on highly active ART. In these patients, supplementalpyridoxine(5–10mgmax/day)isrecommended.
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CHAPTER 5SPECIAL SITUATIONS IN CHILDHOOD TB
5.1 MANAGEMENTOFDRUG-RESISTANTTB(DR-TB)INCHILDRENDrug resistance is aman-madeproblemwhich requires lengthy, complicated and very costlyinterventions.Any formsofdrug resistanceshouldbe treatedonly indesignatedcentres,andin accordance with the National Guidelines on Management of (M) DR-TB. Basic principlesdescribedbelowarementionedforinformationonly.HighexpertiseisrequiredformanagementofDR-TB.Anyfaultinmanagementwillleadtoamplificationofresistanceresultinginnon-treatableDR-TB.
DrugResistantTBshouldbesuspectedifanyofthefeaturesbelowarepresent:
• FeaturesinthesourcecasesuggestiveofDR-TB:
1) Contactwithknowncaseofdrug-resistantTB
2) Remainssmearpositiveafter5monthsoftreatment
3) Historyoftreatmentinterruption
4) HistoryofpreviousTBtreatment
• FeaturesofachildsuspectedofhavingdrugresistantTB:
1) ContactwithknownacaseofdrugresistantTB
2) Treatmentfailuretofirst-linetherapydespitegoodadherence
Mono- and poly-resistanceResistance to isoniazid and/or rifampicin is themost important, as these two drugs form themainstay of current chemotherapy. In the casewheremono-resistance to isoniazid is knownorsuspectedwhentreatmentisinitiated,theadditionofethambutoltoisoniazid,rifampicinandpyrazinamideintheintensivephaseisrecommended.Someauthoritieswouldalsorecommendtheadditionofethambutolinthecontinuationphaselasting6–9months.
Mono-resistancetorifampicinshouldbetreatedwithisoniazid,ethambutolandafluoroquinoloneforatleast12–18months,withtheadditionofpyrazinamideforatleastthefirst2months.AsrifampicinisoneofthepillarsofSCCandresistancetoitcallsforuseofsomesecond-lineanti-TBdrugs,andthecaseshouldbemanagedonlyinspecialcentresforDR-TB,oritrequiresseekingexpertisefromthe centre.
43NationalTuberculosisProgramme
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CHAP
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Multidrugresistanttuberculosis(MDR-TB)MDR-TBisdefinedasresistancetobothisoniazidandrifampicinwithorwithoutresistancetootheranti-TBdrugs.MDR-TBinchildrenismainlytheresultoftransmissionofastrainofM. tuberculosis thatisMDRfromanadultsourcecase,andthereforeoftennotsuspectedunlessahistoryofcontactwithanadultpulmonaryMDR-TBcaseisknown.TheclinicalpresentationofMDR-TBissimilarto thatofdrug-susceptibleTB.Treatment ischallengingandprolongedandspecialist referral isrequired.
MDR-TBshouldbesuspectedinachildwithTB-relatedsymptomswhohas:
• HistoryofprevioustreatmentforTBwithinthepast12months
• ClosecontactwithapersonknowntohaveMDR-TB
• ClosecontactwithaTBcase thathasdied, failedTB treatmentor isnon-adherent toTBtreatment
• Failuretoimproveclinically(persistenceofsymptoms,failuretogainweight)after2-3monthsoffirst-lineTBtreatment,includingpersistenceofpositivesmearorculture
All childrenwith clinically presumptiveMDR-TBshould haveappropriate specimens (sputum,gastric aspirate or lavage, lymph node aspirate) taken for Xpert MTB/RIF, culture and DST.Therefore,anychildwithpresumptiveMDR-TBrequiresreferraltoaspecialistcentreoratleasta district hospital level.
Somebasicprinciplesoftreatmentareasfollows:
• Source case tracing
• Follow the same principles of treatment and regimen as for adults
• Useat least 4drugs towhich theorganism is sensitiveor thepatient haspreviouslynotreceived(naïve)
• UsedailytreatmentonlyandDirectlyobservedtherapy(DOT)isessential
• Counselthechild’scaregiverateveryvisit,toprovidesupport,adviceaboutadverse
events and the importance of compliance and completion of treatment
• Follow-up: clinical, radiological and bacteriological (culture for any child who hadbacteriologicallyconfirmeddiseaseatdiagnosis)
• Treatmentdurationdependsontheextentofthedisease:atleast12monthsafterthelastnegativeculturewithminimaldisease,oratleast18monthsifextensivedisease(lungcavitiesorwidespreadparenchymalinvolvement)
• Do not add a single new drug to a failing regimen
• Treatthechildaccordingtothedrugsusceptibilitypattern(andusingthetreatmenthistory)of
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44 NationalTuberculosisProgramme
thesourcecase’sM. tuberculosis strain if an isolate from the child is not available.
• Balance must be maintained between an effective regimen and the development of adverse events
• Thecommonest serious toxicity ispermanentdeafnessdue to injectableaminoglycoside.With correct dosing, few long term adverse events are otherwise seen with most of the second-linedrugsinchildren,includingethionamideandthefluoroquinolones.
First-lineanti-TBdrugsmaybeusediftheirM. tuberculosisstrain(orthatoftheirsourcecase)isfoundtobesusceptible(e.g.ethambutolandpyrazinamide).Considertheuseofisoniazidandrifampicinfor6monthsifthereisevidencethattheymaybeeffective,i.e.nopriorexposuretothesemedications.Ethambutolisbactericidalathigherdoses,sothatdailydosesupto25mg/kgshouldbeusedinchildrenbeingtreatedforMDR-TB.
5.2 MANAGEMENT OF TB MENINGITIS AND MILIARY TBTBmeningitisandmiliaryTBaremorecommoninyoungchildrenandareassociatedwithhighratesofdeathanddisability,particularly if thediagnosis isdelayed.It isthereforeimportanttoconsider these diagnosis and treatment in young children as early as possible, especially inchildrenwhohaveahistoryofcontactwithanadultwithinfectiousTB.
DiagnosisMiliaryorhaematogenouslydisseminatedTBhasahighrisk(60%-70%)ofmeningealinvolvementand should therefore bemanaged similarly to TBmeningitis. For this reason, many expertsrecommendthatallchildrenwithmiliaryTB(orsuspectedofhavingmiliaryTB)shouldundergoalumbar puncture to test for the presence of meningitis.
TreatmentChildrenwithTBmeningitisormiliaryTBshouldbehospitalized,preferablyforatleastthefirst2months.Levelofserviceforthesecasesisasfollows:
• Districthospitals(firstreferrallevel)
• Tertiary level specialist hospital for further investigations when there is no response totreatment within 2 weeks or there are complications requiring further investigations.
Recommended regimen for treatment of TB meningitis and miliary TB in children
RegimenIntensive Phase Continuation Phase
2HRZE 10HR
45NationalTuberculosisProgramme
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Corticosteroids(usuallyprednisolone)arerecommendedforallchildrenwithTBmeningitisinadosageof2mg/kgdaily for4weeks.Thedoseshould thenbegradually reduced(tapered)over2-4weeksbeforestopping.Thedosageofprednisolonecanbeincreasedto4mg/kgdaily(maximum 60 mg/day) in the case of seriously ill children because rifampicin will decreasecorticosteroidconcentrations,buthigherdosescarryariskofgreaterimmunesuppression.AllchildrenwithpresumptiveorconfirmedTBmeningitisormiliaryTBshouldbehospitalizedinitiallyuntiltheirclinicalstatushasstabilized.ChildrenwithTBmeningitisareathighriskoflong-termdisabilityandthereforebenefitfromspecialistcare,wherethisisavailable.
5.3 TBANDHIVCO-INFECTIONAprovisionalplanisincludedinthisguidelineforinitiationofTBtreatmentinapatientqualifiedforARV,andhowtorecognizeandmanageImmuneReconstitutionInflammatorySyndrome(IRIS)and drug interactions.
PlanshouldbeinaccordancewithGuidelineforclinicalmanagementofHIVinfectioninchildreninMyanmar,3rdedition,NAPMOH2011and5thedition,NAPMOHS2016.
AreasnotaddressedintheguidelineformanagementofHIVshouldbefurtherincooperationwiththeNationalAIDSProgramme(NAP).
For HIV-infected children, comprehensive care involves support for the child and family withappropriate measures to prevent, diagnose and treat opportunistic infections and the use of antiretroviraltherapy.
The steps to assess HIV positive children
• Assess the growth and nutritional status, and need for intervention
• Assess the immunization status and provide appropriate immunizations
(e.g.BCG).AlthoughBCGvaccinationiscontraindicatedwithprovedHIVinfectionstatus,BCGimmunizationatbirthdoseisrecommended.
• Assess for signs and symptoms of OIs and history of exposure to TB. If an OI is suspected, diagnosis and treatment of the OI takes priority over initiation ofART(inparticularforTB).
• AssigntheWHOclinicalstage
• Ensurethatthechildisonco-trimoxazole
• IdentifyconcomitantmedicationsthatmayproducedruginteractionswithART
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46 NationalTuberculosisProgramme
• StageHIVdiseaseusingimmunologicalcriteria
• Perform a CD4 count if available
• CD4%ispreferredinchildren<5yearsandCD4countispreferredinchildren≥5
years
• TocalculatetheCD4%andcount,afullbloodcount(FBC)needstobeperformed
(ideallyautomated)
• TLCisanoptionthatmaybeusedforstartingARTwhereCD4assessmentisnot
available.
• AssesswhetherthechildfulfilsthecriteriaforstartingART
• Proper counselling is important for treatment adherence because non adherence to treatment is the main reason for treatment failure.
• StartingARTisnotanemergencybutoncestartedthetreatmentmustbegiven
ontimeeveryday.Non-adherencetotreatmentisthemainreasonfortreatment
failure.
• Assessthefamilysituationincluding,butnotlimitedto,thenumberofpersonswith
oratriskforHIVinfectionandtheircurrenthealth/treatmentstatus.
• Identify theprimarycaregiver for thechildandhis/herabilityandwillingness to
adheretofollow-upschedulesandtreatmentforHIV,especiallyART.
• IdentifyothercaregiverswhomayberesponsibleforadministeringART.
• Assessfamilymembers’understandingofHIVdiseaseanditstreatment.
• AssessthedisclosurestatusofHIVdiagnosiswithinthefamily(whetherthechild
knowshis/herdiagnosis,whetheranyoneelseknows,andifthechildknowsthe
parent[s]’HIVstatus).
• Assessthefinancialstatusofthefamily,includingtheirabilitytopayfortransportation
to the clinic, afford adequate food/nutritional supplements for the child, pay for
anytreatmentneededandwhethertheyhavearefrigeratorforkeepingARVsthat
need to be stored at a low temperature, if required.
47NationalTuberculosisProgramme
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CHAP
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MostinternationalguidelinesrecommendthatTBinHIV-infectedchildrenshouldbetreatedwitha6-monthregimenasinHIV-uninfectedchildren.Wherepossible,HIV-infectedchildrenshouldbetreatedwithrifampicinfortheentiredurationoftreatment,ashigherrelapseratesamongHIV-infectedadultshavebeen foundwhenethambutol isused in thecontinuationphase.NationalTB Programme, Myanmar recently adapted WHO recommended rapid advice on childhoodTBmanagementusinghighdosepaediatricdrugsandethambutolcontaining4-drugregimen.Therefore,this4-drugregimenmustbeusedforallchildrenwithTB/HIVdualinfection,regardlessoftheirage.MostchildrenwithTB,includingthosewhoareHIV-infected,haveagoodresponsetothe6-monthregimen.Possiblecausesforfailure,suchasnon-compliancewiththerapy,poordrug absorption, drug resistance and alternative diagnoses should be investigated in children whoarenotimprovingonanti-TBtreatment.
AllchildrenwithTBandHIVco-infectionshouldbeevaluatedtodetermine ifARTis indicatedduring the course of treatment for TB. Appropriate arrangements for access to antiretroviral drugs should bemade for patientswhomeet indications for treatment.Given the complexity
Clinical event Clinical diagnosis Definitivediagnosis
LymphnodeTB Nonacute,painless“cold”enlargementoflymphnode,usuallymatted,localizedtooneregion.Mayhavedrainingsinuses.
Responsetostandardanti-TBtreatmentinone month.
ConfirmedbyhistologyorfineneedleaspirateforZiehlNeelsenstain
Culture
PulmonaryTB Non-specificsymptoms,e.g.chroniccough,fever, night sweats, anorexia and weight loss. In the older child also productive coughandhaemoptysis.AbnormalCXR.Responsetostandardanti-TBtreatmentinone month.
Confirmedbypositivesputum smear or culture.
Extrapulmonary/Disseminated TB
Systemicillnessusuallywithprolongedfever, night sweats, weight loss. Clinical features of organs involved, e.g. sterile pyuria,pericarditis,ascites,pleuraleffusion,meningitis, arthritis, orchitis.
Responsetostandardanti-TBtherapy.
ConfirmedbypositivemicroscopyshowingAFBorcultureofMycobacteriumTBfrom blood or other relevant specimen except sputum or BAL.Biopsyandhistology.
PresumptiveanddefinitivecriteriaforrecognizingHIV-relatedTB
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48 NationalTuberculosisProgramme
TB Co-infection in children with HIV
Recommended regimens for children and adolescents initiating ART while on TB treatment ab
Youngerthan3years TripleNRTI(AZT+3TC+ABC)c
3yearsandolder Two NRTIs + EFV ORTripleNRTI(AZT+3TC+ABC)
Recommended regimen for children and infants initiating TB treatment while receiving ART a
Child on standard NNRTIbasedregimen
(TwoNRTIs+EFVorNVP)
Youngerthan3years
Continue NVP, ensuringthatthedoseis200mg/m2OR TripleNRTI(AZT+3TC+ABC)c
3yearsandolder
If the child is receiving EFV, continue the same regimen.If the child is receiving NVP, substitute with EFV.ORTripleNRTI(AZT+3TC+ABC)c
Recommended regimen for children and infants initiating TB treatment while receiving ART a
Child on standard PI based regimen(TwoNRTIs+LPV/r)
Younger than 3years
TripleNRTI(AZT+3TC+ABC)c ORContinue LPV/r, adding RTV to achieve the full therapeutic dose d
3yearsandolder
IfthechildhasnohistoryoffailureofanNNRTI-basedregimen:Substitute with EFV e ORTripleNRTI(AZT+3TC+ABC)c ORContinue LPV/r, adding RTV to achieve the full therapeutic dose d
IfthechildhasahistoryoffailureofanNNRTIbasedregime:TripleNRTI(AZT+3TC+ABC)c ORContinue LPV/r adding RTV to achieve the full therapeutic dose d
Consider consultation with experts for constructing a second line regimen.
of co-administration of anti-TB treatment andART, consultationwith an expert in this area isrecommendedbefore initiationofconcurrent treatment forTBandHIV infection, regardlessofwhichdiseaseappearedfirst.However,initiationoftreatmentforTBshouldnotbedelayed.
Thefollowingtableisanexampleofoutlineforconcurrentmanagementofanti-TBandARTforthe children
49NationalTuberculosisProgramme
Chapter5:SpecialSituationsinChildhoodTB
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a Ensure optimal dosing of rifampicin based on dosing guidelines.
b Substitute ARV drugs based on an age appropriate ART regimen in line with nationallyrecommendedfirstlineART.
cTripleNRTI isonlyrecommendedfor thedurationofTBtreatment;anage-appropriatePIorNNRTIbasedregimenshouldberestartedwhenrifampicinbasedtherapyends.
dIncreaseRTVuntilitreachesthesamedoseasLPVinmg,inaratioof1:1.
eSubstitutionofEFVshouldbeconsideredasthepreferredoptionandEFVcouldbemaintainedafterTBtreatmentendstoenablesimplificationandharmonizationwiththeARVdrugregimensused for older children.
Note:
- ThereisnodruginteractionbetweenNRTIsandrifampicin.
- Apartfromrifampicin,otheranti-TBdrugsdonotinteractwithARVdrugs.
- Anti-TBdrugsandNNRTIs(especiallyNVP)canhaveoverlappinghepatotoxicity;therefore,close monitoring of liver functions is required.
- RifampicinlowersthedruglevelofNVPby20%-58%andthatofEFVby25%.Inchildren,thereisnoinformationontheappropriatedosageofNVPandEFVwhenusedwithrifampicin.StandarddosageregimensofEFVcanbeused.
- Rifampicinisthemostpotentanti-TBdrugandshouldbepartofananti-TBregimen,especiallyduringthefirst2monthsoftreatment.Changingfromarifampicin-basedtoanon-rifampicin-based regimen during the maintenance phase depends on the discretion of the treating physicianandshouldfollowthenationalTBtreatmentguidelines.However,non-rifampicincontainingmaintenance-phaseanti-TBtherapyhasbeenshowntohavelowerefficacy.
- IfTBisdiagnosedfirst,anti-TBtreatmentshouldbestartedandARTshouldbestarted
2–8weeksafteranti-TBtreatmenttoensurethatthetreatmentistoleratedandtodecreasetheriskofimmunereconstitutioninflammatorysyndrome(IRIS).
- AZTord4T+3TC+ABChavenodruginteractionwithrifampicin.However,thiscombinationhasbeenshowntobelesspotentinonestudyinadultsthan2NRTI+EFV.
- ABCisexpensiveandisthereforenotreadilyavailable.
- Aftercompletionofrifampicin-basedtreatment,considerswitchingtreatmenttostandardfirstlineregimenwith2NRTIs+NVPorEFV.
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50 NationalTuberculosisProgramme
Criteria for imitating, discontinuing and monitoring Cotrimoxazole preventive therapy
Age Criteria for initiation Criteria for discontinuation a
HIV exposed infant
Givetoallexposedinfants,startingat4-6weeksafterbirth
UntiltheriskofHIVtransmissionendsorHIVinfectionisexcluded.
Children and adolescents with HIV
InitiateallregardlessofWHOclinicalstage or CD4 count.
As a priority, initiate to those:Alllessthan5yearsofage;Allolderthan5yearsofagewithsevereHIVdisease(State3or4)orCD4count<350cells/mm3
Maybediscontinuedin5yearsof age and older who are clinicallystable,withevidenceofimmunerecoveryband/orviralsuppressiononART.
CotrimoxazoleChildrenwithTBandHIVco-infectionshouldalsoreceiveCotrimoxazoleasprophylaxisforotherinfectionslikePneumocysticjiroveciiPneumonia(PCP).
a Discontinue if the person has Stevens- Johnson syndrome, severe liver disease, severeanaemia,severepancytopeniaornegativeHIVstatus.
bParameterforimmunerecoveryinchildrenwhen>5yearsold:CD4cellcount>350cells/mm3,with viral load suppression
Note:(HIVexposedinfant)
• DefinedasachildborntoanHIV-infectedmotherorchildbreastfeedingfromanHIV-infectedmotheruntilHIVexposurestops(6weeksaftercompletecessationofbreastfeeding)andinfection can be excluded.
• Inchildrenunder18monthsHIVinfectioncanonlybeconfirmedbyvirologicaltesting.
Dose:150mgTMP/750mgSMXperm2threetimesperweek(foraninfantof6weeks,givehalfatabletofcotrimoxazole"80/400"tablet)
51NationalTuberculosisProgramme
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52 NationalTuberculosisProgramme
CHAPTER 6RECORDING AND REPORTING
Notification of children with TB has already been included in the routine NTP recording andreportingsystem.ItiscrucialtonotifytheNTPofallidentifiedTBcasesinchildren,registerthemfor treatment and record their treatment outcome. At the end of the treatment course for each child,thetownshipTBcoordinatorshouldrecordtheoutcomeinthetownshipTB-register.
Definitionsofstandardtreatmentoutcomes
Outcome Definition
Cured ApulmonaryTBpatientwithbacteriologicallyconfirmedTBatthebeginning of treatment who was smear or culture negative in the last month of treatment and on at least one previous occasion.
Treatment completed A TB patient who completed treatment without evidence of failure but with no record to show that sputum smear or culture results in the last month of treatment and on at least one previous occasion were negative, either because tests were not done or because results are unavailable.
Treatment failure A TB patient whose sputum smear or culture is positive at month 5 or later during treatment.
Died ATBpatientwhodiesforanyreasonbeforestartingorduringthecourse of treatment.
Lost to follow up A TB patient who did not start treatment or whose treatment was interrupted for 2 consecutive months or more.
Notevaluated A TB patient for whom no treatment outcome is assigned. This includescases“transferredout”toanothertreatmentunitas well as cases for whom the treatment outcome is unknown to the reporting unit
Treatment success The sum of cured and treatment completed.
53NationalTuberculosisProgramme
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CHAP
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The townshipTB coordinator compiles and sends the township quarterly reports of all casesregisteredand their treatment outcomes to theStateandRegionalTBofficer.TheStateandRegionalTBofficerverifiesthatthetownshipreportsarecorrect,completeandconsistent,andcompilesandsubmitsaStateandRegionreporttothecentralNTP.Recordingandreportingtwoagegroupsforchildren(0–4yearsand5–14years)inthetownshipTBregistersisusefultoorderanti-TBdrugs(inchild-friendly formulations foryoungchildren)and tomonitor trendsofcase-findingandtreatmentoutcomes(seeTablebelow).
ExamplesofindicatorsinroutineNationalTBprogramme(NTP)recordingandreporting
Indicator Significance Benchmark or target
Proportion of all TB cases
which are in children
Mayindicateoverorunder
reporting of TB cases in children.
10-15%
Proportion of children who
arecured(smearpositive
TB)orcompletetreatment
(smearnegativepulmonary
TBandextrapulmonaryTB)
Demonstratesthequalityor
management of children with
TBintheNTP.
>90%
Proportion of children with
miliaryTBorTBmeningitis
Thisproportionshouldbeverylow
whereBCGvaccinationcoverageishigh.
If<2yearsago:10%
If>3yearsago:<1%
CohortanalysisisthekeymanagementtoolforevaluatingtheeffectivenessoftheNTP.Acohortisagroupofpatientsdiagnosedandregisteredfortreatmentduringaspecifictimeperiod(usually3months).Justasevaluationoftreatmentoutcomeinnewsmear-positivepulmonaryTBpatientsisusedasastandardindicatorofNTPqualityforadultpatients,evaluationoftreatmentoutcomebycohortanalysisinchildrenisavaluableindicatorofprogrammequalityforchildhoodTBpatients.
Paediatricians at hospital level are responsible to record and report TB cases detected among children,usingspecificNTPformats(refertoAnnex4).
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54 NationalTuberculosisProgramme
CHAPTER 7ROLES AND RESPONSIBILITIES
ChildrenwhoaresuspectedofhavingorarediagnosedwithTBmaybemanagedbyoneormoreofarangeofdifferentcareproviderswithvaryinglevelsofexpertiseandexperience,includingprimarycarestaff,generalcliniciansandpaediatricians.Inordertoprovidethebestcaretothesechildren,itisessentialtoclarifyrolesandresponsibilitiesofthoseinvolvedintheirmanagement.AllprovidersofTBcareshouldmanageTBpatientsinconjunctionwiththeNTP.
Levels of careAs the diagnosis of TB in children should require a minimum of tests service delivery withstructured case management is recommended as described in the following tables.
55NationalTuberculosisProgramme
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CHAP
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Leve
ls o
f car
e
Staf
fM
inim
um re
quire
men
tsR
espo
nsib
ilitie
sA
ctio
ns
Prim
arycare
leve
l
This
leve
l in
clud
es ru
ral
and
urba
n he
alth
cen
tres
(RHCand
UHC)
Bas
ic h
ealth
st
aff a
nd
gene
ral
prac
titio
ners
Recognizethesymptom
sand
sign
s of
chi
ldho
od T
B
Recognizethesignificanceof
hous
ehol
d co
ntac
t with
sm
ear
posi
tive
sour
ce c
ases
Identifychildrenwithsym
ptom
sand
sign
s su
gges
tive
of T
B a
s w
ell a
s contactsofnew
lydiagnosedsource
cases(usuallyadultswithsputum
smearpositivepulmonaryTB
).
InliaisonwiththeNTP,arrange
treatment(directlyobservedtherapy)
for c
hild
ren
with
infe
ctio
n or
dis
ease
an
d en
sure
refe
rral
s an
d fo
llow
up
are
carr
ied
out.
Referchildtotownshiphospital
whichisthefirstreferrallevelofcare.
Manageminoradverseevents.
Firs
t lev
el o
f ca
re
This
leve
l in
clud
es
tow
nshi
p an
d di
stric
t ho
spita
ls
Medical
officersand
paed
iatri
cian
s
Exa
min
e ch
ildre
n su
spec
ted
of
havi
ng T
B
Havegoodqualityreportedchest
radi
ogra
ph a
vaila
ble
HIVtestingandcounselling
(atdistrictlevel)
Spu
tum
sm
ear e
xam
inat
ion
Dia
gnos
e M
. tub
ercu
losi
s in
fect
ion
andTB
diseasebybeingabletotake
ahistory,performaphysical
exam
inat
ion
and
inte
rpre
t the
followingtests:
Sputumsmearm
icroscopy
CXR
MakethediagnosisofTBin
unco
mpl
icat
ed c
ases
RegisterthecaseswiththeNTP
Treatcasesappropriately
(FollowNationalG
uidelines)
Referbacktoprim
arycarelevelfor
cont
inua
tion
of tr
eatm
ent
Refercom
plicatedcasestoStateor
RegionalH
ospital
Managemajoradverseevents.
RevisedNationalGuidelinesonManagementofTuberculosisinChildrenRevisedNationalGuidelinesonManagementofTuberculosisinChildren
56 NationalTuberculosisProgramme
Leve
ls o
f car
e
Staf
fM
inim
um re
quire
men
tsR
espo
nsib
ilitie
sA
ctio
ns
Sec
ond
leve
l of
care
This
incl
udes
S
tate
and
Regional
hosp
itals
.
Per
son
with
ex
perti
se in
m
anag
ing
com
plic
ated
TB
Spu
tum
sm
ear e
xam
inat
ion
Che
st ra
diog
raph
Tube
rcul
in s
kin
test
LPandpleuralfluidaspiration
Ultr
asou
nd fo
r abd
omen
Biopsy,Fineneedleaspirationfor
TB g
land
s of
nec
k
HIVtestingandcounselling
Dia
gnos
e an
d m
anag
e co
mpl
icat
ed
TB, i
nclu
ding
mos
t cas
es o
f di
ssem
inat
ed T
B a
nd T
B m
enin
gitis
MakethediagnosisofTBin
com
plic
ated
cas
es
Initiatetherapy
Referbacktothetownshiplevel
for r
egis
tratio
n an
d co
ntin
uatio
n of
tre
atm
ent
Refermorecomplicatedcasesto
tertiarycarelevelhospitals
Managemajoradverseevents
Tertiarylevelof
care
This
incl
udes
te
achi
ng
hosp
itals
.
Per
son
with
ex
perti
se in
m
anag
ing
com
plic
ated
TB
Spu
tum
sm
ear e
xam
inat
ion
Che
st ra
diog
raph
Tube
rcul
in s
kin
test
LPandpleuralfluidaspiration
Ultr
asou
nd fo
r abd
omen
and
hea
rt
Biopsy/Fineneedleaspirationfor
TB g
land
s of
nec
k
HIVtestingandcounselling
Add
ition
al in
vest
igat
ions
Dia
gnos
e an
d m
anag
e co
mpl
icat
ed
TB, i
nclu
ding
mos
t cas
es o
f di
ssem
inat
ed T
B a
nd T
B m
enin
gitis
.
ChildrenwithMDR-TBcaretobe
managedonlyindesignated(M)
DR-TBtreatmentcentres.
Sup
port
the
othe
r lev
els
of c
are
in
the
diag
nosi
s an
d m
anag
emen
t of
the
mos
t sev
ere
and
com
plic
ated
fo
rms
of c
hild
hood
TB
ReferthepatienttoTow
nshiplevelto
regi
ster
in T
B re
gist
er.
ProvideadvicetotheNTP
regarding
child
hood
TB
issu
es.
Managemajoradverseevents.
57NationalTuberculosisProgramme
Chapter7:RolesandResponsibilities
CHAP
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7
Steps of referral
Refer to next HF level
Reasons for referral Minimal investigation availableRHC
TSP HC/hospital
District hospital
State/Regional hospital
Tertiary level
Sputum smear examination, CXR
Plus gastric asp. TST, LP, pleural aspiration,Echocardiogram, US
Plus CT scan, bronchoscopy
TB suspects
Diagnosis uncertain orcomplicated cases in needfor Further assessment
Complicated cases orcases not respondingto treatment
Complicated cases requiring highly Specialized treatmentor investigations
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58 NationalTuberculosisProgramme
ANNEXES
ANNEX 1Procedures for Obtaining Clinical Samples for Smear Microscopy and Gastric Aspiration ProceduresThis annex reviews the basic procedures for the more common methods of obtaining clinical samples from children for smear microscopy: expectoration, gastric aspiration and sputuminduction.
Procedure of Sputum Induction
Sputuminduction(SI)shouldbedoneinanegative-pressureisolationroomusedonlyforthattask, or at least in a room with doors open. Staff protection measures include use of appropriate respiratoryprotectionmasks(e.gN95masks),limitationoftimespentintheroomduringprocedureand use of standard hospital procedure for staff exposed to TB.
SI is undertaken preferably on a (2-3 hour) fasting child, or at least it is not performed aftermealsorsnacks.Thechildrenareencouragedtocleantheirmouthandremovedebris.Theyarepre-treatedwith200µgofsalbutamolviametered-doseinhalerwithattachedspacertopreventbronchoconstriction.Childrenwithasthmaoroxygensaturationof≤94%shouldnotundergoSI.
SIcanbedoneusingajet-nebulizerdrivenpreferablybyoxygenwithaflowrateof5-6litres/minorbyamotor-drivenaircompressor(asimplenebulizer).Itcanalsobedonewithanultrasonicnebulizer.Hypertonic saline (either 3%or 5%) is usedas solution for nebulized inhalation toinduce sputum production.
With jet-nebulizer5mlof sterilehypertonic saline isgiven for15minutes.Withanultrasonicnebulizer 5-10 ml of sterile hypertonic saline is given for 10 -20 minutes. Thereafter chestpercussionwasdoneoveranteriorandposteriorchestwall.Sputumisobtainedbycoughingifthechildcancooperateorbysuctioningthroughnasopharynxororopharynxwithasterilemucusextractorofcatheter-size6or7.Aminimumsampleof3ml isconsideredadequate.Childrenshouldbewatchedfor1-2hoursafterprocedureforanycomplication.
Allnebulizerequipmentwasdecontaminatedaftereachsessionbythoroughwashingandsoakinginglutaraldehydeovernight.
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1. A. Expectoration
Background
Allsputumspecimensproducedbychildrenshouldbesent forsmearmicroscopyand,whereavailable, mycobacterial culture and Xpert MTB/RIF. Children who can produce a sputumspecimenmaybeinfectious,so,aswithadults,theyshouldbeaskedtodothisoutsideandnotinenclosedspaces(suchastoilets)unlessthereisaroomespeciallyequippedforthispurpose.Threesputumspecimensshouldbeobtained:anon-the-spotspecimen(atfirstevaluation),anearlymorningspecimenandasecondon-the-spotspecimen(atfollowupvisit).
Procedure
Givethechildconfidencebyexplainingtohimorher(andanyfamilymembers)thereasonforsputum collection.
Instruct the child to rinse his or her mouth with water before producing the specimen. This will help toremovefoodandanycontaminatingbacteriainthemouth.
Instruct the child to take two deep breaths, holding the breath for a few seconds after each inhalationandthenexhalingslowly.Askhimorhertobreatheinathirdtimeandthenforcefullyblow the air out. Ask him or her to breathe in again and then cough. This should produce sputum from deep in the lungs. Ask the child to hold the sputum container close to the lips and to spit into itgentlyafteraproductivecough.
Iftheamountofsputumisinsufficient,encouragethepatienttocoughagainuntilasatisfactoryspecimenisobtained.Rememberthatmanypatientscannotproducesputumfromdeepintherespiratorytrackinonlyafewminutes.Givethechildsufficienttimetoproduceanexpectorationwhichheorshefeelsisproducedbyadeepcough.
If there is no expectoration, consider the container used and dispose of it in the appropriate manner.
1. B. Gastric aspiration
Background
ChildrenwithTBmay swallowmucuswhich containsM. tuberculosis.Gastric aspiration is atechniqueusedtocollectgastriccontents to try toconfirmthediagnosisofTBbymicroscopyandmycobacterial culturebya laboratoryunderquality control of theNationalTBReferenceLaboratory(NTRL).Becauseofthedistresscausedtothechild,andthegenerallylowyieldofsmearpositivityonmicroscopy, thisprocedureshouldonlybeusedwhereculture isavailableaswellasmicroscopy.Microscopycansometimesgivefalse-positiveresults(especiallyinHIVinfectedchildrenwhoareatriskofhavingnontuberculousmycobacteria).Cultureenablesthedeterminationofthesusceptibilityoftheorganismtoanti-TBdrugs.
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Gastricaspiratesareusedforcollectionofsamplesformicroscopyandmycobacterialculturesinyoungchildrenwhensputacannotbespontaneouslyexpectoratednorinducedusinghypertonicsaline.It ismostusefulforyounghospitalizedchildren.However,thediagnosticyield(positiveculture)ofasetof threegastricaspirates isonlyabout25–50%ofchildrenwithactiveTB,soanegativesmearorcultureneverexcludesTBinachild.GastricaspiratesarecollectedfromyoungchildrensuspectedofhavingpulmonaryTB.Duringsleep,thelung’smucociliarysystembeats mucus up into the throat. The mucus is swallowed and remains in the stomach until the stomachempties.Therefore,thehighestyieldspecimensareobtainedfirstthinginthemorning.
Gastricaspirationoneachofthreeconsecutivemorningsshouldbeperformedforeachpatient.Thisisthenumberthatseemstomaximizeyieldofsmearpositivity.
Of note, the first gastric aspirate has the highest yield. Performing the test properly usuallyrequirestwopeople(onedoingthetestandanassistant).Childrennotfastingforatleast4hours(3hours for infants)prior to theprocedureandchildrenwitha lowplatelet countorbleedingtendencyshouldnotundergotheprocedure.
Thefollowingequipmentisneeded:
• Gloves
• Nasogastrictube(usually10Frenchorlarger)
• 5,10,20or30cm3syringe,withappropriateconnectorforthenasogastrictube
• Litmus paper
• Specimen container
• Pen(tolabelspecimens)
• Laboratoryrequisitionforms
• Sterilewaterornormalsaline(0.9%NaCl)
• Sodiumbicarbonatesolution(8%)
• Alcohol/chlorhexidine.
Procedure
Theprocedurecanbecarriedoutasaninpatientfirstthinginthemorningwhenthechildwakesup, at the child’s bedside or in a procedure roomon theward (if one is available), or as anoutpatient(providedthatthefacilityisproperlyequipped).
Thechildshouldhavefastedforatleast4hours(infantsfor3hours)beforetheprocedure.Findan assistant to help.
Prepare all equipment before starting the procedure.
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Position the child on his or her back or side. The assistant should help to hold the child.
Measurethedistancebetweenthenoseandstomach,toestimatedistancethatwillberequiredto insert the tube into the stomach.
Attachasyringetothenasogastrictube.
Gentlyinsertthenasogastrictubethroughthenoseandadvanceitintothestomach.
Withdraw(aspirate)gastriccontents(2–5ml)usingthesyringeattachedtothenasogastrictube.
Tocheckthatthepositionofthetubeiscorrect,testthegastriccontentswithlitmuspaper:bluelitmusturnsred(inresponsetotheacidicstomachcontents).Thiscanalsobecheckedbypushingsomeair(e.g.3–5ml)fromthesyringeintothestomachandlisteningwithastethoscopeoverthe stomach.
Ifnofluidisaspirated,insert5–10mlsterilewaterornormalsalineandattempttoaspirateagain.
Ifstillunsuccessful,attemptthisagain(evenifthenasogastrictubeisinanincorrectpositionandwaterornormalsalineisinsertedintotheairways,theriskofadverseeventsisstillverysmall).
Do not repeat more than three times.
Withdrawthegastriccontents(ideallyatleast5–10ml).
Transfergastricfluid from thesyringe intoasterilecontainer (sputumcollectioncup).Addanequalvolumeofsodiumbicarbonatesolutiontothespecimen(inordertoneutralizetheacidicgastriccontentsandsopreventdestructionoftuberclebacilli).
After the procedure
Wipethespecimencontainerwithalcohol/chlorhexidinetopreventcross-infectionandlabelthecontainer.
1. Filloutthelaboratoryrequisitionforms.
2. Transportthespecimen(inacoolbox)tothelaboratoryforprocessingassoonaspossible(within4hours).
3. Ifitislikelytotakemorethan4hoursforthespecimenstobetransported,placethemintherefrigerator(4–8°C)andstoreuntiltransported.
4. Givethechildhisorherusualfood.
Safety
Gastricaspirationisgenerallynotanaerosolgeneratingprocedure.Asyoungchildrenarealsoatlow risk of transmitting infection, gastric aspiration can be considered a low risk procedure for TB transmissionandcansafelybeperformedatthechild’sbedsideorinaroutineprocedureroom.
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ANNEX 2Administering, Reading and Interpreting Tuberculin SkinTestATST is the intradermal injection of a combination ofmycobacterial antigenswhich elicit animmune response (delayed type hypersensitivity), represented by induration, which can bemeasuredinmillimeters.TheTSTusingtheMantouxmethodisthestandardmethodofidentifyingpeople infected with M. tuberculosis.Multiplepuncture testsshouldnotbeused todeterminewhetheraperson is infected,as these testsareunreliable (because theamountof tuberculininjectedintradermallycannotbepreciselycontrolled).
Detailsofhowtoadminister,readandinterpretaTSTaregivenbelow,using5tuberculinunits(TU)oftuberculinPPDs.Analternativeto5TUoftuberculinPPDsis2TUoftuberculinPPDRT23.
Administration
1. Locateandcleaninjectionsite5–10cm(2–4inches)belowelbowjoint
• Placeforearmpalmsideuponafirm,well-litsurface
• Selectanareafreeofbarriers(e.g.scars,sores)toplacingandreading.
• Cleantheareawithalcoholandletitcompletelydry
2. Preparesyringe
• CheckexpirationdateonvialandensurevialcontainstuberculinPPDs(5TUper0.1ml)
• Useasingledosetuberculinsyringewithashort(¼to½inch)27-gaugeneedlewithashort bevel
• Fillthesyringewith0.1mltuberculin
3. Injecttuberculin
• Inserttheneedleslowly,bevelup,atanangleof5–15°
• Needlebevelshouldbevisiblejustbelowskinsurface
4. Check injection site
• Afterinjection,aflatintradermalwhealof8–10mmdiametershouldappear.Ifnot,repeattheinjectionatasiteatleast5cm(2inches)awayfromtheoriginalsite.
5. Recordinformation
• Recordalltheinformationrequiredbyyourinstitutionfordocumentation(e.g.dateandtimeoftestadministration,injectionsitelocation,lotnumberoftuberculin).
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Reading
The results should be read between 48 and 72 hours after administration. A patient who does not returnwithin72hourswillprobablyneedtoberescheduledforanotherTST.
1. Inspect site
• Visuallyinspectinjectionsiteundergoodlight,andmeasureinduration(thickeningoftheskin),noterythema(reddeningoftheskin).
2. Palpate induration
• Usefingertipstofindmarginsofinduration.
3. Markinduration
• Usefingertipsasaguideformarkingwidestedgesofindurationacrosstheforearm.
4. Measurediameterofindurationusingaclearflexibleruler
• Place“0”ofrulerlineontheinsideleftedgeoftheinduration.
• Read ruler line on the inside right edge of the induration (use lowermeasurement ifbetweentwogradationsonmmscale).
5. Recorddiameterofinduration
• Donotrecordas“positive”or“negative”.
• Onlyrecordmeasurementinmillimetres.
• If no induration, record as 0 mm.
Interpretation
TSTinterpretationdependsontwofactors:
• Diameter of the induration;
• Person’sriskofbeinginfectedwithTBandriskofprogressiontodiseaseifinfected.
• Diameterofindurationof≥5mmisconsideredpositivein:
• HIVinfectedchildren
• Severelymalnourishedchildren(withclinicalevidenceofmarasmusorkwashiorkor).
• Diameterofindurationof≥10mmisconsideredpositivein:
• Allotherchildren(whetherornottheyhavereceivedBCGvaccination).
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Causes of false negative and false positive TSTs are listed in the table below
Causes of false negative TST Causes of false positive TST
• Incorrect administration or interpretation of test
• Incorrect interpretation of test
• HIV • BCGvaccination
• Improper storage of tuberculin • Infectionwithnon-tuberculousmycobacteria
• Viralinfections(e.g.measles,varicella)
• Vaccinatedwithliveviralvaccines(within6weeks)
• Malnutrition
• Bacterial infections (e.g.typhoid,leprosy,pertussis)
• Immunosuppressive medications (e.g.corticosteroids)
• Neonatalpatient
• Primaryimmunodeficiency
• Diseaseoflymphoidtissue(e.g.Hodgkindisease,lymphoma,leukaemia,sarcoidosis)
• Low protein states
• Severe TB
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Thetableprovidedforconstructingcurvesareinyearsforagebasedindicators(horizontalaxis),kgforweightbasedindicator(verticalleftaxis).Percentilesareshownontherightsideofthecart(verticalrightaxis).
ANNEX3
WEIGHT CHART
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Boys
Boys
Thetableprovidedforconstructingcurvesisinyearsforagebasedindicators(horizontalaxis),kgforweightbasedindicator(verticalleftaxis).Percentilesareshownontherightsideofthechart(verticalrightaxis).
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Girls
Girls
Ann
ex 4
Rec
ordi
ng a
nd R
epor
ting
Form
s
ISO
NIA
ZID
PR
EVEN
TIVE
TH
ERA
PY C
AR
D
HealthFacility_________________Township________________District____________Region/State____________
Nam
e__________________________Age________Sex_______Address_________________________________
Mother’name____________________ContacttownshipTB
num
ber____________
IPTstartingdate:__/__/____dailydose______Expectedstopdate__/__/____
Datecompletionpreventivetreatment__/__/____
Day
Month
12
34
56
78
910
1112
1314
1516
1718
1920
2122
2324
2526
2728
2930
31No
dose
s this
mo
nthBo
dy w
eight
(kg)
Rema
rks
(side
effec
ts,
trans
fer ou
t, an
y pro
blem,
sp
ecify
)
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ISO
NIA
ZID
PR
EVEN
TIVE
TH
ERA
PY R
EGIS
TER
Hospital_______________
Township_____________
District_____________Region/State_____________
Ser
ial
No
Nam
eA
geS
exA
ddre
ssC
onta
ct
townshipTB
No
Dat
e st
art I
PT
Dat
e st
op IP
TRem
arks
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REFERENCES
• Global tuberculosis control: WHO report 2015: World Health Organization, Geneva,Switzerland,2015
• Guidance for national tuberculosis programmes on the management of tuberculosis inchildren–secondedition.WorldHealthOrganization,Geneva,Switzerland,2014
• GuidelinefortheclinicalmanagementofHIVinfectioninchildreninMyanmar,NAPMOH,2011
• ManualforHealthstaffonTuberculosisControlinMyanmar,NTPMOH2006
• TB/HIVaclinicalmanual,2nded.Geneva,WorldHealthOrganization,2004 (WHO/HTM/TB/2004.329)
• TheStopTBStrategy.Geneva,WorldHealthOrganization,2003(WHO/HTM/TB/2006.368)
• Treatmentoftuberculosis:guidelinesfornationalprogrammes,4rded.Geneva,WorldHealthOrganization,2009(WHO/HTM/TB/2009.420)
• Rapid advice: treatment of tuberculosis in children, World Health Organization, Geneva,Switzerland,2010(WHO/HTM/TB/2010.13)
• Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy forpeoplelivingwithHIVinresourceconstrainedsetting,WorldHealthOrganization,Geneva,Switzerland,2011
• Policy statement: automated real-time nucleic acid amplification technology for rapid andsimultaneous detection of tuberculosis and rifampicin resistance: XpertMTB/RIF system,WorldHealthOrganization,Geneva,Switzerland,2011(WHO/HTM/TB/2011.4).
• Managementofmultidrug-resistanttuberculosisinchildren:afieldguide.Boston,USA:TheSentinelProjectforPaediatricDrug-ResistantTuberculosis;March2015,Secondedition
• GuidelinefortheclinicalmanagementofHIVinfectioninMyanmar,5thedition,2016.
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