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THE UNITED REPUBLIC OF TANZANIA
MINISTRYOFHEALTH,COMMUNITYDEVELOPMENT,GENDER,ELDERLYANDCHILDREN
NATIONALGUIDELINESFORTHEMANAGEMENTOFTUBERCULOSISINCHILDREN
NATIONALTUBERCULOSISANDLEPROSYPROGRAMME
(NTLP)Third Edition, 2016
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TABLEOFCONTENTS
ABBREVIATIONS.....................................................................................................................................5
AKNOWLEDGEMENTS............................................................................................................................6
FOREWORD............................................................................................................................................7
1 GENERALINFORMATIONABOUTTUBERCULOSISINCHILDREN....................................................8
1.1 Epidemiologyoftuberculosisinchildren:globallyandinTanzania......................................8
1.2 Tuberculosisinchildrenandtheneedforspecificguidelines...............................................8
1.3 Naturalhistoryandpathogenesisoftuberculosis...............................................................9
2 DIAGNOSISOFTUBERCULOSISDISEASEINCHILDREN.................................................................12
2.1 Pulmonarytuberculosis.......................................................................................................13
2.2 Diagnosisofextrapulmonarytuberculosis..........................................................................19
2.3 Classificationbasedonanatomicalsiteofdisease..................................................................25
3 MANAGEMENTOFTUBERCULOSISDISEASEINCHILDREN..........................................................27
3.1 Treatmentregimensfortuberculosisdisease......................................................................27
3.2 Medicationsanddosages....................................................................................................28
3.3 Fixed-dosecombinationtablets...........................................................................................28
3.4 Practicalguidanceforadministeringmedicinestochildren................................................29
3.5 Steroidusefortuberculosis..................................................................................................30
3.6 Managementofadversereactionstoanti-tuberculosismedications.................................30
3.7 Managementofcutaeneousreactions................................................................................31
3.8 Managementofdrug-inducedhepa t i t i s ..........................................................................32
3.9 Monitoringtreatmentanddirectlyobservedtherapy........................................................33
3.10 Clinicalandbacteriologicresponse................................................................................34
3.11 Treatmentfailure(confirmingfailureandmanagement).....................................................35
3.12 Managingtreatmentinterruption.......................................................................................35
3.13 Ancillaryandsupportivecare................................................................................................36
3.14 Nutritionforchildrenwithtuberculosis ..........................................................................36
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3.15 Counselingforchildrenwithtuberculosis...........................................................................37
4 PREVENTIONOFTUBERCULOSISINCHILDREN............................................................................40
4.1 BacilleCalmette-Guérinimmunisation...............................................................................40
4.2 ManagementoflatentTBinfectioninchildren...................................................................41
4.3 Tuberculosisinfectioncontrol.............................................................................................45
5 PAEDIATRICTUBERCULOSISINSPECIALSITUATIONS..................................................................46
5.1 TB/HIVinchildren.............................................................................................................46
5.2 Drug-resistanttuberculosisinchildren................................................................................52
6 RECORDING,REPORTINGANDUSEOFDATAFORCHILDRENWITHTUBERCULOSIS..................58
6.1 Introduction.........................................................................................................................58
6.2 TBRecordingandReportingToolsinChildren....................................................................58
6.3 RecordingandReportingofOutcomesofChildTBCases...................................................60
7 ROLESANDRESPONSIBILITIESOFTHEHEALTHSYSTEMINDIAGNOSISANDMANAGEMENTOFCHILDRENWITHTUBERCULOSIS..........................................................................................................64
7.1 Introduction.........................................................................................................................64
7.2 CommunityLevelTBcare....................................................................................................64
7.3 HealthfacilitylevelTBcare..................................................................................................64
7.4 IntegrationofTBservicesintoReproductiveandChildHealthservices.............................65
ANNEX1: SPUTUMINDUCTION...................................................................................................66
ANNEX2: GASTRICASPIRATION......................................................................................................68
ANNEX3: DIAGNOSISANDMANAGEMENTOFMALNUTRITION.................................................70
ANNEX4: DrugRe-introductionChallengefollowingdrug-inducedhepatitisforchildrenbasedonweight-bands.................................................................................................................................72
ANNEX5: DIAGNOSISOFHIVINFECTIONININFANTSANDCHILDRENLESSTHAN18MONTHS....74
ANNEX6: TUBERCULOSISSCREENINGANDIPTELIGIBILITYTOOLFORUSEWITHHIV/AIDSPATIENTS.............................................................................................................................76
ANNEX7: TUBERCULOSISDIAGNOSTICTOOLSANDTHEIMPACTOFHIVONTHEIRINTERPRETATION.................................................................................................................................80
ANNEX8: CAUSESOFLUNGDISEASEINHIV-INFECTEDINFANTSANDCHILDREN.......................81
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References..........................................................................................................................................83
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ABBREVIATIONS
AFB Acid-fastbacillusAIDS AcquiredImmuneDeficiencySyndromeALT AlanineaminotransferaseART AntiretroviraltherapyAST AspartateaminotransferaseBCG BacilleCalmette-GuérinCDC UnitedStatesCentersforDiseaseControlandPreventionCPT CotrimoxazolepreventivetherapyCSF CerebralspinalfluidCT ComputedtomographyCTC CareandtreatmentclinicCTRL CentralTuberculosisReferenceLaboratoryCXR Chestx-rayDOT DirectlyobservedtherapyDST DrugsusceptibilitytestingDTLC DistrictTuberculosisandLeprosyCoordinatorFDC Fixed-dosecombinationHIV HumanImmunodeficiencyVirusIGRA InterferongammareleaseassayIPT IsoniazidpreventivetreatmentIRIS ImmuneReconstitutionInflammatorySyndromeLFT LiverfunctiontestLTBI LatenttuberculosisinfectionMDRTB Multidrug-resistanttuberculosisMoHCDGEC MinistryofHealth,CommunityDevelopment,Gender,ElderlyandChildrenMRI MagneticresonanceimagingNTLP NationalTuberculosisandLeprosyProgrammePATH ProgramforAppropriateTechnologyinHealthRTLC RegionalTuberculosisandLeprosyCoordinatorRUTF Ready-to-usetherapeuticfoodTB TuberculosisTSH Thyroid-stimulatinghormoneTST TuberculinskintestWHO WorldHealthOrganization
Anti-tuberculosisdrugabbreviationsE EthambutolH IsoniazidPAS Para-aminosalicylicacidR RifampicinS StreptomycinZ Pyrazinamide
HIVdrugabbreviations3TC LamivudineABC AbacavirAZT ZidovudineEFV EfavirenzLPV/r Lopinavir/ritonavirNRTI NucleosidereversetranscriptaseinhibitorNNRTINon-
nucleosidereversetranscriptaseinhibitorNVPNevirapine
SMZ SulfamethoxazoleTMP Trimethoprim
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ACKNOWLEDGEMENTS
The National guidelines for the management of Tuberculosis in children is the result of collective efforts and strong commitment from Ministry of Health, Community Development, Gender, Elderly and Children and partner institutions working within and outside the country. The Ministry wishes to thank the Centre for Disease control (CDC) for providing both funding and technical support for reviewing of the guideline.
Special gratitude is extended to NTLP staff for their tireless efforts and oversight in review the review process notably Dr Beatrice Mutayoba, Dr Wanze Kohi, Dr Deus Kamara, Lilian Ishengoma, Emmanuel Nkilligi, Dr Zuweina Kondo, Dr Johnson Lyimo and Jumanne Mkumbo as well as NACP staff Dr Werner Maokola and Dr Irene Massawe.
In addition, the Ministry acknowledges the technical support from implementing partners KNCV (Dr Willy Mbawala) , BAYLOR(Dr Jason Bacha), MNH (Dr Richard Christopher), EGPAF(Dr Stella Kassone), I-TECH( Mr Patrick), NIMR-Mbeya (Dr Issa Sabi), Dr Michael Irira (KCMC) and PATH (USA) who allowed their staff to participate fully and work hand in hand to review and update the National Guidelines for the management of Tuberculosis in children .
Dr. Neema Rusibamayila
Director of Preventive Services
January, 2017
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FOREWORD
According to the Ministry of health, Community Development, Gender, Elderly and Children (MoHCDGEC) – NTLP annual reports, the notification for childhood TB for the past 4 years is approximately 10 percent of all TB cases notified in the country. WHO has estimated in epidemic countries including Tanzania, almost 15% – 20% of notified TB cases are likely to be children . The first guideline was developed in 2012 and was then revised in 2013.
The revision of the Guidelines for the management of Tuberculosis in children follows evidence that has been generated globally from randomized controlled trials, observational studies, operational research, and best practices from programmatic implementation. TB alliance has introduced and launched a new pediatric formulation which will be adopted by many countries including Tanzania. This new formulation is believed to have better adherence by both mothers and children.
The revised guidelines demonstrate the commitment of the Ministry to fight against tuberculosis in children in order to reduce morbidity and mortality. National TB and Leprosy Programme (NTLP), the National AIDS Control Programme (NACP), and other stakeholders will work synergistically to reduce the burden of TB/HIV co-infection.
The Ministry engaged a wide range of stakeholders that participated in a lengthy process to revise the document. The principles presented here reflect the substantial input, informed expert opinions, content, and quality of work that were contributed by all of the stakeholders throughout this process.
The Ministry is satisfied that this document reflects national and international standards for guidelines. Because of the extensive process to involve a wide range of stakeholders and various organizations, the Ministry is confident that the appropriate implementation of the guidelines will bring the anticipated positive impact for children affected by the TB and HIV epidemics.
It is important to note that this policy is just one dimension of the Government of Tanzania’s efforts to combat the dual epidemics and should not be regarded as a panacea to the TB and HIV epidemics. Other dimensions that the Government of Tanzania is considering include increasing the availability of resources to implement the policy, supporting the 7ilitary7ion7l structure through which the policy guidelines will be practiced, developing the overall management system of collaborative TB/HIV activities, and supporting a system of policy implementation as well as actual service delivery.
Finally, it is the hope of the MoHCDGEC that every one of the stakeholders will effectively comply with the policy guidelines. Let everyone play their part and it will be accomplished.
Prof. Muhammad Bakari Kambi Chief Medical Officer January, 2017
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1 GENERALINFORMATIONABOUTTUBERCULOSISINCHILDREN
1.1 Epidemiologyoftuberculosisinchildren:globallyandinTanzania
Tuberculosis (TB) is among the top 10 causes of illness and death among childrenworldwide.Globallyin2015,therewereanestimated10.4millionincidentcasesofTB.Among those1.0million (10%)were children. In2015,WHOestimated that TBkilled1.4millionpeoplewith anadditional of 0.4milliondeathsdue to TBamongpeoplelivingwithHIV.
ThemagnitudeofTBdiseaseamongstchildreninTanzaniaisdifficulttoascertaindueto challenges of diagnosis and reporting. However, data from the NTLP show thatpaediatriccaseswere5,699(9.4%)ofallcasesnotifiedin2015.AstheoverallincidenceofTBinfectionisdecreasinginTanzania,thegreaternumberofpaediatricdiagnoseslikelyreflectsimprovementsinrecognitionofthediseaseinchildren.(SeeFiqures1.1and1.2onthefollowingpage)
1.2 Tuberculosisinchildrenandtheneedforspecificguidelines
Despiteseveralinterventionswhichhavebeenmade,stillthereisgradualincreaseofTBcasenotificationamongchildren.InfantsandyoungchildrenarehighlysusceptibletoTB.ThediagnosisofpulmonaryTB(PTB)inchildrenisacommonclinicalchallengebecause of the atypical nature of TB symptoms and the rapid progression of TBinfection to TB disease. Bacteriological confirmation is also rarely possible andaccording to the NTLP report of 2015, bacteriological confirmed pulmonary TB inchildren aged <15 years accounted for 9.3% of all reported paediatric TB cases.Significant number of cases of TB in children are missed and remain undetectedbecause of the diagnostic challenges thereby contributing to the high TB relatedmorbidity and mortality in this age group. These challenges include, lack ofknowledge and skills amonghealth careworkers to detect andmanage TB inchildren, under utilization of screening tools , unavailability of diagnostic tools,inadequatecontacttracingandinsufficientoperationalresearchinthisarea.Thispeadiatric guideline has been developed to guide the health care workers onpromptmanagementofTBinchildren.
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Figure1.1.ProportionofchildrenamongstnewTBcasesnotified;2006to2015
Figure1.2Trendsinpaediatric(<15years)Tbcasenotification(newcases);2006to2015
Accordingtothedrugresistancesurveyconductedin2006/2007amongstsmear-positivenotifiedcases,theprevalenceofmultidrug-resistanttuberculosis(MDRTB) inTanzaniawas1.1percentand3.1percentamongstnewandretreatedTBcases respectively. In 2014, therewere an estimated 600MDR TB cases in thecountryandonly34MDRTBcaseswerenotified(NTLPdata,2014).NoavailabledataforchildrenwithMDRTB;thisislargelyattributedbydifficultiesindiagnosis.
1.3 Naturalhistoryandpathogenesisoftuberculosis
Tuberculosis is caused by Mycobacterium tuberculosis, an acid-fast bacillus
0.0% 1.0% 2.0% 3.0% 4.0% 5.0% 6.0% 7.0% 8.0% 9.0%
10.0% 11.0%
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
% o
f <15
yea
rs o
ld
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
num
ber o
f pea
diat
ric T
B ExtraPulmonary
Smear negative
Smear positive
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(AFB).Achildisexposedtothetuberclebacilliwhenincontactwithanadultoradolescent with infectious TB (AFB smear positive). Upon inhalation, thetubercle bacilli are deposited in the lungs and multiply initially within theterminalalveoli.Thisprimary lesion iscalledaGhonfocus.Someofthebacilliare phagocytosed but not killed by macrophages that carry the organismsthrough lymphatic channels to the regional lymph nodes, mainly in the hilarregion.Lymphaticandhaematogenousspreadofthebacillitoalmostanyorganin the body can occur and cause disseminated disease such asmeningitis or10ilitarydisease.
The incubation period between when tubercle bacilli are inhaled and thedevelopmentofdelayedhypersensitivityinchildrenismostoften4to8weeks.Thisisdemonstratedbythedevelopmentofapositivetuberculinskintest(TST,also called aMantoux test). In themajority of children infected, the immuneresponsestopsthemultiplicationofM.tuberculosisbacilliatthisstageandtheinfectionremainslatentformanyyears,possiblyalifetime.Childrenwithlatenttuberculosisinfection(LTBI)havenosignsorsymptomsofTBdisease.However,reactivation TBmay occur in individualswith aweak immune system due tomalnutrition, malignancy, chronic or recurrent infections, or HIV/AIDS. Insomeindividuals,theimmuneresponseisnotsufficienttocontaintheprimaryinfection and disease occurs within a few months. Progression to disease ishighestinthefirst6monthsafterinfectionbutremainshighfor2years.Riskofprogressionisincreasedwhenprimaryinfectionoccursbeforeadolescence(lessthan 10 years of age)—particularly in the very young (0–4 years)—and inimmunocompromised children. Diagnosis of TB disease in young childrenrepresentsrecenttransmissionofM.tuberculosis,andeffortsshouldbemadeto identify and treat the source case (usually an adult in the household or afamilymember).
Most childrenwho develop TB disease experience pulmonarymanifestations.Young children (lessthanage4) and immunosuppressed children can developcomplicatedandunusual formsof intrathoracicTBdue toalteredordeficientimmuneresponsestoM.tuberculosis.Childrenyoungerthan10yearsgenerallyhave paucibacillary disease and a nonproductive cough. Thus, they present alowriskfortransmissionofinfectiontoothers.However,childrenwithlaryngealdiseasecanbeinfectious,evenataveryyoungage.
Infants and children less than 2 years are at very high risk for progressionfrom LTBI to TBdiseasedue to their immature immune systems.Once thesechildrendevelopTBdisease,theyaremorelikelytorapidlyprogresstoamoreseriousformofTB,suchasTBmeningitisor10ilitary(disseminated)TB.Theseforms can be life threatening and therefore always warrant immediateevaluationandinitiationoftherapy.Childreninthisagegroupoftenhavenon-specificsymptomssuchaslossofappetite,poorweightgainorweightloss,andlethargy.
M. tuberculosis is a slow-growing organism, so long treatment courses arenecessary to achieve eradication. Treatment also requires the use of multiple
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antibioticstopreventthedevelopmentofdrug-resistantstrains.Duetothelengthandcomplexityoftreatmentregimens,pooradherencetomedicationisabarriertosuccessfultreatment.Useoffixed-dosecombinations(FDCs)anddirectlyobservedtherapy(DOT)programsgreatlyimproveoutcomes.
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2 DIAGNOSISOFTUBERCULOSISDISEASEINCHILDREN
Diagnosing TB disease in children is challenging because it is difficult toachieve bacteriologic confirmation. The diagnosis therefore combines ahistory of exposure to an infectious TB source, clinical presentation, andlaboratoryandradiologicexaminations.
To evaluate a child suspected of having TB, the MoHCDGEC recommendsconductingthefollowing:
• Complete history, including a history of TB contact and symptomsconsistentwithTBdisease.
• Clinical examination and use of a scoring chart (including growthassessment)tolookforthevarioussignsofTBdisease.
• Tuberculinskintestwheneveravailable.
• Bacteriologicconfirmationwheneverpossible.
• Investigations relevant for suspected pulmonary and extra-pulmonaryTB,includingchestradiographyforpulmonaryTB.
• HIVtestingforallTBsuspects.
All findingsmustbe considered carefully,butwhenahistoryof close contactwithacaseofTB,especiallyaninfectious(smear+/MTB+)case,ispresent,thisstronglysupportsadiagnosisofTBinachild,especiallyinthoseyoungerthan5years.
Bacteriologic confirmation is achievable in only about 30 – 40% of cases;therefore,adiagnosisofTB(pulmonaryorextra-pulmonary)inachildisoftenbasedonthepresenceoftheclassictetrad:
1. Historyofclosecontactwithaninfectiouscase(AFBsmear+orMTB+).
2. SignsandsymptomsofTBdiseasefromhistoryandphysicalexamination.
3. ApositiveTST.
4. Suggestive findings of TB disease on indicated laboratory or radiologicinvestigations (chest radiograph, fine needle aspiration, spinalradiograph,abdominalultrasound,etc.).
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2.1 Pulmonarytuberculosis
Clinicalpresentationininfants
InfantswithpulmonaryTBaremorelikelytobesymptomaticbecauseoftheirsmallairwaydiametersrelativetotheparenchymalandlymphnodechanges.The most common pulmonary symptoms are nonproductive cough anddifficultybreathing.Systemicsymptomssuchas fever,anorexia,poorweightgain,weight loss, and failure to thrivemayalsooccur. InfantswithTBoftenpresentasacaseofseverepneumoniawith fastbreathing,chest indrawing,and respiratory distress. Infants may present with decreased activity,increasedirritabilityorlethargy.
Clinicalpresentationinchildren
Pulmonary disease and associated intra-thoracic (hilar) adenopathy are themostfrequentfindingsofTBinpreschoolandschool-agedchildren.CommonsymptomsofpulmonaryTBinchildreninthisagegroupinclude:
• HistoryofclosecontactwithTB.
• Coughfor2ormoreweeks(oranycoughforHIV-positivechildren).
• Fever for atleast 2 weeks without other obvious cause and not improvingwithantibiotics/antimalarials.
• Weightloss,weightfaltering,failuretogainweight,orfailuretothrive.
• Reducedactivityandirritability.
Althoughthesesymptomsarenonspecific,theirpresencesupportsadiagnosisofpulmonaryTB.
There are no specific features on clinical examination that can confirm thatthe presenting illness is due to pulmonary TB. However, persistent fever(temperature>38°Cdailyformorethan14days),chroniccoughthatdoesnotrespondtoantibiotics,andfailuretogainweightarecommon.
Clinicalpresentationinadolescents
ThepresentationofpulmonaryTBinadolescentsissimilartothepresentationinadults.ThetypicalsymptomsofTB—coughlastingmorethan2weeks,feverfor 2 ormoreweeks,weight loss, anorexia,malaise, excessive night sweats,chestpain,andhaemoptysisaremorelikelytobepresentinadolescentsthaninchildren.
Clinicalassessment
TakingagoodmedicalhistoryisthefirststeptodiagnosingTBinachild.Askthepatientorcaregivertodescribe:
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• Whensymptomsstarted.
• Aboutappetiteandweightgainorloss.
• Historyofcoughing,orcoughingblood.
• HistoryofTBcontact.
• OthermedicalconditionsthatpredisposetoTB,suchasHIV.
• Fever/coughwhichisnotrespondingtonormalantibiotics
• Historyofreducedactivitiesand/orirritability
• HistoryanddetailsofanypriorTBdisease/treatment.
Performathoroughphysicalexaminationtoassess:
• Appearance:thinorwasted.
• Temperature:normalorelevated.
• Lymphnodes:enlarged,painless,maybemattedorwithdischargingsinus.
• Chest:
§ Respiratoryratemaybenormalorhigh.
§ Trachea:maybedisplacedinmassivepleuraleffusions.
§ Breathsoundsmaybenormal,buttheremaybebronchialbreathing,crepitations
§ (crackles),rales,andwheezing.
§ Dullnessonpercussion(inthecaseofpleuraleffusions).
§ Distantheartsoundsinpericardialeffusion.
• Abdomen:masses,ascites,ordistension.
• Joints:maybeswollenorwitheffusion;angulationofthespine(Gibbus)
Specimencollection
In children of all ages with presumptive pulmonary TB, sputum should becollectedforAFBmicroscopy.Sputumspecimensmaybecollectedbymeansofexpectoration, sputum induction, or gastric aspiration. In many cases,laboratory confirmation is difficult to establish because pulmonary TB inchildren is typically paucibacillary and specimensmay be difficult to obtain.Nonetheless,attemptbacteriologicconfirmationforallpresumptivecases.
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Expectoratedsputum
Obtaining expectorated sputum from children younger than 5 yearsmay bedifficult, while most adolescents can produce expectorated sputumspontaneously. In children, examination of expectorated sputum has a lowyield (<15%for AFB smear positivity and <30% for positive mycobacterialculture). For childrenwhoare able toproduce sputum, send two specimensfor smear microscopy. Collect one spot specimen at the visit and give aspecimencup to theparentor caregiver andexplainhow to collect anearlymorning specimen the following day and bring it to the clinic. Collect anadditional specimen for mycobacterial culture when indicated. Sputuminduction orgastric aspiration (described below) can be used to obtainspecimensinchildrenunabletoexpectorate.
Inducedsputum
Sputuminduction is thepreferredmethodforcollectingsputumfromyoungchildren who are not able to expectorate. Induced sputum has a higherdiagnosticyieldthanexpectoratedsputuminchildrenandiscomparabletoorbetter than inpatientgastricaspirate specimens. It is a safeandeffectiveprocedureinchildrenasyoungas1monthofageincentreswithadequatetrainingand15ilitary15ioequipment.Itisrecommendedthatthisprocedurebe performed at district, regional, and zonal referral hospitals whereappropriateequipmentisavailable,andbytrainedpersonnelwhoareabletorespondtoanycomplications.Sendtwospotsamplesforanalysis.(SeeAnnex1foradescriptionoftheprocedure.)
Gastricaspiration
Gastricaspirationusinganasogastric feeding tube shouldbeused toobtainmaterial for smear and culture from young children who are unwilling orunabletoexpectoratesputum.
Earlymorning gastric contents contain sputum swallowed during the night.Thechildshouldbehospitalizedandtwoearlymorningsamplescollectedondifferent days before the child eats, drinks, or gets out of bed, to 15ilitaryspecimenyield.
Note:Gastric aspiration should only be undertaken where culture facilitiesareavailablenearbybecauseculturespecimensneedtobeprocessedwithin4 hours of collection because the acidic juices in the stomachwill kill thebacteria quickly. It is recommended that this procedure be performed atdistrict,regional,andreferralhospitalsbytrainedpersonnel.(SeeAnnex2foradescriptionoftheprocedure.)
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Diagnosticmethods
Smear
ConventionallightmicroscopyusingZiehl-Neelsen(ZN)stainedsmearsandlight-emittingdiodefluorescencemicroscopyarethemaindiagnostictestsforTBwidelyavailableinTanzania.
Culture
Mycobacterial culture is more sensitive than smear; however, Tbbacilligrowth on traditional solid media requires 4 to 8 weeks and in liquidculture systems requires 2 to 4 weeks. Currently in Tanzania, culture isavailable in the following referral laboratories: Central TuberculosisReference Laboratory (CTRL, Muhimbili National Hospital), BugandoMedical Centre, Kilimanjaro Christian Medical Centre, Dodoma ReferralHospital, Kibong’oto National Tuberculosis Hospital, Southern highlandsZonalHospital (MbeyaZonalReferralHospital),andPembaPublicHealthLaboratory.
Always send sputum for culture and sensitivity in retreatment cases. Forchildren who are not retreatment cases, culture should be done at thediscretionoftheTBclinicwherethediagnosticwork-upoccurs.Inthesecases,specimentransportwillneedtobearranged inconsultationwith themedicalofficerinchargeofthefacility.
Otherdiagnostictests
Xpert® MTB/RIF is now available in in Tanzania for rapid TB diagnosis anddetectionof rifampicin resistance. It isasemi-automatedpolymerasechainreaction test that can be used on sputum samples. At least two sputumsamplesarerecommended.
Lineprobeassaytechnology,suchastheHaintest,isavailableinTanzania,atthe CTRL, NIMR-Mbeya, NIMR –Mwanza, Kibong’oto National TB HospitalandDodomaRegionalReferralHospitalforrapiddetectionofdrugresistance.
Other serum tests such as ESR or blood counts and serological test are notsensitiveorspecificenoughandarethereforenotrecommendedfordiagnosisofTB.
ThetuberculinskintestisintendedfordiagnosisofLTBI,butapositiveTSTcanbeusedasanadjuncttoolduringinvestigationforthediagnosisofTBdiseasein children. Criteria for a positive TST are provided in Table 2.1. However, apositive TST alone is never diagnostic of TBdisease, as it only indicates TBexposure.
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Table2.1.InterpretationofTSTresultsPatient characteristic Positive TST result HIV infected ≥5 mm diameter induration Severely malnourished (marasmus or kwashiorkor) ≥5 mm diameter induration Contact to a case of infectious TB (smear positive) ≥5 mm diameter induration All other children (regardless of whether they have received a Bacille Calmette-Guérin vaccination or not)
≥10 mm diameter induration
False-positive resultscanoccur frompriorvaccinationwithBacilleCalmette-Guérin (BCG), infection with non-tuberculous mycobacteria, and improperadministrationorinterpretation.Similarly,anegativeTSTdoesnotruleoutTBdisease, since false-negative results can occur in the following situations:incorrectadministrationorinterpretationoftheTST,agelessthan6months,severemalnutrition,advancedHIVdisease,immunosuppressionbydiseaseormedication, certain viral illnesses or recent live-virus 17ilitary17ion, or evenoverwhelmingTBdisease.
Contraindications to TST administration are a previous severe or blisteringreactiontotuberculinorapreviouspositiveresult.SeeSection4,“Preventionoftuberculosisinchildren,”formoredetails.
Bloodtestssuchaserythrocytesedimentationrateorbloodcounts(e.g.,fullbloodpicture) todiagnoseanaemiaarenot recommendedbecause theyarenotspecifictoTB.
Chestradiography
Obtainchestradiography(anterio-posteriorand lateralviews)onallchildrensuspectedtohavepulmonaryTB.IndicationsforachestX-rayinclude:
• Coughnotrespondingtonormalantibiotics andpresentformorethan2weeks(orany
coughinHIV-positivechildren).
• Feverformorethan2weekswithoutothersource.
• ConcernsofextrapulmonaryTB(tolookforconcomitantpulmonaryTB).
• PresumptiveTuberculosiswithnegativesmears.
Most children with pulmonary TB will have abnormal findings on chestradiography. Themost common chest radiograph findings in a child with TBdiseaseinclude:
• Perihilar,peritracheal,orsubcarinallymphadenopathy.
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• Persistentopacification(anylobe).
• Advancedadenopathycausingbronchialcompressionleadingtosecondaryinfectionorlungco l lapse.
• A18ilitarypatternofopacifications.
• Otheropacificationthatdoesnotimproveorresolvefollowingacourseofantibiotics.
Adolescents with TB generally present with typical adult disease findings ofupperlobeinfiltrates,pleuraleffusions,andcavitationsonachestradiograph.
Clinicaldiagnosisintheabsenceofbacteriologicconfirmation
Tuberculosis in children is often diagnosed clinically because bacteriologicconfirmation,whenavailable, isonlyachievable inabout30to40percentofcases (Figure 2.1 provides an algorithm for diagnosing pulmonary TB inchildren). In the absence of bacteriologic confirmation, use the “Score ChartforDiagnosisofTB inChildren”(Table2.2) forclinicaldiagnosis.Referachildwithascoreof7ormoreforTBtreatment.
Table 2.2. Score Chart for Diagnosis of TB in Children*
SCOREIFSIGNORSYMPTOMPRESENT 0 1 2 3 4 Score Generalfeatures Duration of illness Less than 2
weeks 2-4 weeks More than 4 weeks
Failure to thrive or weight loss Weight gain No weight gain or
weight faltering
Weight loss
TB contact None Reported (butno documentation) smear-negative orEPTB
Smear positive (with documentation)
TST Negative, not done Positive
Malnutrition not improved after four weeks of therapy Present
Unexplained fever not responding to appropriate therapy
Positive
Localfeatures
Chest x-ray TB-suggestive features like infiltration, cavity, or hillar lymph nodes
Painless, enlarged lymph nodes
Any non- cervical lymph nodes
Positive cervical lymph nodes
Swelling of bones or joints Positive
Unexplained ascites or abdominal mass
Positive
Central nervous system findings: meningitis*, lethargy, irritability and other behavior changes
Positive
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Angle deformity of the spine Positive
TOTALSCOREAscoreof7ormoreindicatesahighlikelihoodofTB.ReferthechildforTBtreatment. *Meningitis not responding to conventional antibiotics. Other causes of meningitis e.g bacterial must be excluded
HIV infection, sickle cell disease, or rheumatologic diseases alone (in the absence of TB disease) can cause scores of >7. Therefore, best clinical judgment must be used when using this scoring system (see Section 5.1, “TB/HIV in children” for further guidelines). Do not use aminoglycosides and fluoroquinolones, as they are active against M. tuberculosis complex and, thus, may cause transient improvement in persons with TB.
Scoring adapted from: Edwards K. The diagnosis of childhood tuberculosis. P N G Med J. 1987;30(2):169-178.
Figure 2.1. Algorithm for diagnosing pulmonary TB in children younger than 6years
NOTES 1. Other conditions might include cardiac disease, congenital lung disease,fungal infections (including
pneumocystis pneumonia), and chronic lung diseases such as asthma or bronchiectasis, parasitic infections, or oncologicdisease.
2. Nutritional support may include nutritional 19ilitary19i, provision of supplemental or therapeutic feeds. 3. Antibiotics should treat common causes of chest bacterial infections. Consider continuing with other
investigations if child has already received antibiotics without improvement. Avoidaminoglycosidesandfluoroquinolones,astheyhaveanti-Tbeffects.
Diagnosisofextrapulmonarytuberculosis
The clinical presentation of extrapulmonary TB depends on the site ofdisease. Themost common formsof extrapulmonarydisease in childrenare
VIS
IT 1
VIS
IT 3
Algorithm for Diagnosing Pulmonary TB in Children below 6 years old
VIS
IT 2
Presumptive TB
· Collect 2 sputum specimen (spot-morning or spot-spot)· If sputum specimen is not available, do gastric lavage· Offer HIV test (PITC) if status unknown
Xpert if not available smear microscopy
MTB +/Smear positive · MTB -/Smear negative· Unable to collect sputum specimen
· Start TB treatment· Provide nutritional supports· HIV care if applicable
Use "Score Chart for Diagnosis of TB in Children"
Score < 7 Score > 7
TB unlikely· Investigation for other conditions¹· OfferHIVtestifnotperformed· Givebroadspetrumantibioticsandantinalarials(ifnotyetgiven)ᶟ· Givenutritionalsupport(ifneeded)²· Dochest-x
· Start TB Treatment· Provide nutritional
support²· HIV care if applicable
Symptoms Resolved If symptoms persist
TB unlikelyRepeat "Score Chart for
Diagnosis of TB in Children"
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TB of the superficial lymph nodes and of the central nervous system.Neonateshavethehighestriskof20ilitaryTBandTBmeningitis.
Todiagnose extrapulmonary TB, collect specimens for smear and/or culturefromanysitewherediseaseissuspected.Themostcommonextrapulmonaryspecimens include tissue specimens such as lymph node or bone,cerebrospinalfluid,urine,bonemarrow,andpleuralfluid.
If any child suspected having extrapulmonary TB is also coughing, performinvestigationsforpulmonaryTB(sputum,chestradiography)accordingtotheguidelinesintheprevioussection.
Tuberculosislymphadenitis
Tuberculosislymphadenitistypicallypresentswith:
• Painless,fixed,matted,enlargedlymphnodes,especiallyinthecervicalregion,withorwithoutfistulaformation.
• Enlargednodespersistingforseveralweeksandnotassociatedwithsymptomsofupperrespiratoryinfection,ortheyremainoncetherespiratorysymptomshaveresolved.
Perform fine needle aspiration of a superficial lymph node. If this is notfeasible or is non-diagnostic, perform an excisional biopsy (refer to thenearest regionalhospital if theprocedure isnotavailableatyoursite).Sendthe specimen for AFB smear microscopy, culture, and histopathologyexamination. The presence of caseating granulomas on histopathology ishighlysuggestiveofTB.
Intheabsenceofapositivesmearorcultureresult,withorwithoutsuggestivehistopathology findings, a clinical diagnosis may be made using the ScoreChartforDiagnosisofTBinChildren(Table2.2).
Tuberculousmeningitis
TheclinicalpresentationofTBmeningitisdependsontheageofthechildandthestageofthedisease.Theevolutionofsymptomsisusuallygradualoveraperiodof3weeks.Occasionallytheonsetisabrupt.
First stage: Personality/Behaviour change, irritability, anorexia, listlessness,fever.
Secondstage(after1to2weeks):Presentswithtypicalmeningitissymptomsof headache, neck pain, neck stiffness, fever, lethargy, and convulsionsresultingfromincreasedintracranialpressureanddamagetothebrain.
Third stage: Loss of consciousness, irregular pulse and respirations, risingfever,anddeath.
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Tuberculous meningitis should be suspected in cases of meningitis notresponding to antibiotic treatment, with subacute onset, cranial nerveinvolvement, communicating hydrocephalus, stroke, and/ or elevatedintracranialpressure. If therearenosignsof increased intracranialpressure,perform a lumbar puncture to obtain cerebral spinal fluid (CSF) for whiteblood cell count (total and differential), protein, glucose, AFB smearmicroscopy,andmycobacterialculture.
IntheCSFofachildwithTBmeningitis,duringearlystages,thewhitebloodcell count reveals a high proportion of neutrophils; later, there is a greaterproportion of lymphocytes. CSF glucose is at the lower limit of normal, andprotein initially isnormalbut risessteadily toveryhighconcentrations.YieldfromCSFAFBsmearmicroscopyisusuallylow.
If TB meningitis is suspected, start treatment immediately. Do not delaytreatmentwhilewaiting forCSF smears and culture results.Wherepossible,performserialexaminationoftheCSFforAFBsmearmicroscopyandcultureto improve definitive diagnosis. Culture has the highest yield of diagnosticconfirmation.Where available,molecular diagnostic techniques such as lineprobeassayandXpert®MTB/RIFcanalsobeperformedonCSFtoconfirmthepresenceofM.tuberculosis,thoughitssensitivityisnotwellstudied.
If smear and culture are not available, CSF findings of low glucoseconcentration, elevatedprotein, and elevated lymphocytes are suggestive ofTB meningitis. If these are present and TB meningitis is suspected, starttreatmentimmediately,evenintheabsenceofbacteriologicconfirmation.
InthesettingofTBmeningitisandaneurologicaldeficit,performaCTscanorMRI of the head to diagnose tuberculomas, infarcts, vasculitis, andhydrocephalus.Chestradiographymayrevealpulmonaryinvolvementormaybenormal.
Miliary/Disseminatedtuberculosis
MiliaryordisseminatedTBismorecommoninveryyoungchildren(age2andyounger).Childrenusuallypresentveryill,appearingwithfailuretothrive,lethargy,lossofappetite,weightloss/failure togainweight,andinseverecases, coma. Signs and symptoms of TB meningitis may be present, asdissemination to themeninges and central nervous system is common, andthese two conditions often present concomitantly (in approximately 30percentofcases).Mycobacterialdisseminationtomajororganscanresult inmulti-organ failure and sepsis. Consider diagnosis of disseminated TB inpatientswithpoorresponsetoantibioticsforpresumedsepsis.
Performalumbarpuncturetolookforevidenceofdisseminated/21ilitaryTB.The patient is usually too ill to provide sputum specimens. Perform a chestradiograph, as it may show the characteristic scattered millet seed pattern(seebelow).Duetothehighriskofdeathordisabilityfrom21ilitaryTB,start
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treatmentimmediately.
Pleuraltuberculosis
Pleuraleffusionisexcessfluidthataccumulatesinthepleuralspace.Excessiveamountsoffluidcanimpairbreathingbylimitingtheexpansionofthelungsduringrespiration.Signsandsymptomsinclude:
• Coughing,fastbreathing,andchestindrawing.
• Stonydullness topercussion, decreasedair entry, decreased tactile andvocalfremitus,anddiminishedchestexcursionontheaffectedside.
• Displacementofthetracheaandcardiacapextothecontralateralside.
Homogeneous opacification of the whole hemithorax or obliteration of thecostophrenicangleinsmalleffusion.
Performapleuraltapforlaboratoryanalysis:glucose,protein,andwhitebloodcell count with differential. Fluid is usually yellow (straw coloured), withelevated protein and lymphocyte levels. Bloody fluid or pus indicates otherconditions. Send fluid for AFB smearand mycobacterial culture. Cultureprovides greater diagnosis. Pleural biopsy may show granulomas onhistopathology.
Pericardialtuberculosis
Pericardial effusion is excess fluid that accumulates in the pericardial space.Excessive amounts of fluid can impair efficient cardiac function. Signs andsymptomsinclude:
• Dullacheintheleftchest.
• Abdominalpain.
• Shortnessofbreath,fatigue,andcoldextremitiesinseverecases.
When skilled 22ilitary22 are available, perform a pericardial tap, preferablywithultrasoundguidance,andsendthefluidfor laboratoryanalysis:glucose,protein, and white blood cell count with differential. If infected with M.tuberculosis, pericardial fluid usually has elevated protein and lymphocytelevels.SendfluidforAFBsmearandmycobacterialculture.Smearmicroscopyislowyield,andcultureprovidesgreaterdiagnosis.
Abdominaltuberculosis
Tuberculosiscaninvolveanypartofthegastrointestinaltractandcanresultinenlargedandmattedmesentericlymphnodes;ulcers,fibrosis,orstricturesofthe bowel wall; and peritoneal tuberculomas. Ascites (excess fluid in theperitonealcavity) isalso possible. Themostcommonsiteof involvement is
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theileocecalregion,andcanpresentwithapalpablemass intheright lowerquadrantand/orsignsofobstruction,perforation,ormalabsorption.
Perform an abdominal ultrasound or CT scan to evaluate forlymphadenopathy, tuberculomas, or fibrosis. In cases of ascites, perform anascetictapforlaboratoryanalysis:glucose,protein,andwhitebloodcellcountwith differential. Expect infected fluid to have elevated protein andlymphocytelevels.Sendfluidformycobacterialculture.
Tuberculosisofthespine/bones/joints
Tuberculosisdiseaseofthespine,bones,orjoints(osteoarticularTB)typicallyoccurswithin6 to36monthsofprimary infection.Themost commonsite isthe spine (also called Potts Disease), followed by the knee, hip, and anklejoints.ThefollowingsignssuggestTBinthebonesorjoints:
• Acuteonsetofangulationofthespine(Gibbusdeformity).
• Progressiveweaknessoflimbs.
• Jointeffusions.
• Progressivediseasemayresultinjointdestructionwithorwithoutabscessorsinusformation.
• Retropharyngealmass(coldabscessfrominfectedcervicalvertebra).
• Psoasabscess(coldabscessfrominfectedlumbarvertebra).
Perform a radiograph of the affected area, with review by a radiologist. Inpatients with joint effusions, perform a joint tap for laboratory analysis:protein,whitebloodcellcountwithdifferential,AFBsmear,andmycobacterialculture.Synovialbiopsymayshowcharacteristicgranulomaformation.
Neonataltuberculosis
Congenital TB is when the neonate acquires TB in utero throughhaematogenous spread via the umbilical vessels, or at the time of deliverythrough aspiration or ingestion of infected amniotic fluid or cervico-vaginalsecretions.NeonatalTBiswhenthenewbornisinfectedafterbirthbybeingexposed to an infectious caseof TB,which is usually themotherormaybeanother close contact. It is often difficult to distinguish between congenitalandneonatalTB,andmanagement is the same forboth.Both formswillbereferredtohereasneonatalTB.
The TB-exposed neonatemay be asymptomatic or symptomatic. Symptomsand signs of TB in the neonate are usually nonspecific and include thefollowing:
• Lethargy.
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• Poorfeeding.
• Lowbirthweightandpoorweightgain.
• Respiratorydistress.
• Non-resolvingpneumonia.
• Hepatosplenomegaly.
• Lymphadenopathy.
• Abdominaldistensionwithascites.
• Aclinicalpictureof“neonatalsepsis”withdisseminatedTB.
ThediagnosisofneonatalTBshouldbeincludedinthedifferentialdiagnosisofchronic neonatal infection with a poor response to antimicrobial therapy,congenitalinfections,andatypicalpneumonia.Themostimportantcluetothediagnosis of TB in the newborn is a maternal history of TB or TB/HIV co-infection.
Thefollowinginvestigationsshouldbecarriedout:
• Tuberculinskintest.
• Chestradiography.
• Lumbarpuncture.
• Blood,CSF,andgastricaspiratecultures,performedpromptly.
• Ifpossible,examinationoftheplacentahistologicallyforgranulomataandAFB,andcultureofaspecimenforM.tuberculosis.
DisseminatedBacilleCalmette-Guérindisease
Prolonged fever or other systemic symptoms in an HIV-infected or HIV-unknowninfantwithinweeksormonthsofBCG24ilitary24ionshouldraisetheindex of suspicion for life-threatening disseminated BCG,which occurs in asmany as 1 percent of HIV-infected infants. Perform a complete physicalexamination,asmany infantswillalsohavesignsof localBCGdisease,whichincludesswelling,redness,ulcerationattheinjectionsite,andenlargedaxillarylymphnodes.
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Table2.3.SummaryofinvestigationsforExtrapulmonaryTB
Anatomicalsite
Recommendedinvestigations
TB adenitis (especially from cervical region) Lymph node biopsy or fine needle aspiration; sputum if coughing.
Miliary TB Sputum and chest x-ray. Perform additional diagnostic tests as appropriate for associated symptoms and signs (e.g., lumbar puncture to test for meningitis).
TB meningitis
Lumbar puncture (cerebrospinal fluid for white blood cell count with differential; biochemical analysis for protein and glucose concentration, Xpert® MTB/RIF where available, AFB smear and mycobacterial culture; chest x-ray and sputum.
Pleural effusion Chest x-ray, pleural tap for biochemical analysis (protein and glucose concentration, white blood cell count, Xpert® MTB/RIF where available, AFB smear and mycobacterial culture, sputum.
Abdominal TB
Abdominal ultrasound and 25ilitar tap for white blood cell count total and differential; biochemical analysis for protein and glucose concentration, Xpert® MTB/RIF where available, AFB smear and mycobacterial culture; sputum and chest x-ray if coughing.
TB of the spine/bones/joints (osteoarticular TB)
x-ray, joint tap for white blood cell count total and differential; biochemical analysis for protein and glucose concentration, Xpert® MTB/RIF where available, AFB smear and mycobacterial culture; synovial biopsy; sputum if coughing.
Pericardial TB
Chest x-ray, chest ultrasound, pericardial tap for white blood cell count total and differential; biochemical analysis for protein and glucose concentration, Xpert® MTB/RIF where available, AFB smear and mycobacterial culture; sputum if coughing.
Neonatal TB
Chest x-ray, lumbar puncture, cerebrospinal fluid and gastric aspirates, Xpert® MTB/RIF where available; for AFB smear and mycobacterial cultures, histopathology examination of the placenta for AFB and granulomata; evaluation of mother for TB.
Drug-resistant TB any anatomical site Mycobacterial culture and DST of relevant specimens.
2.3 Classificationbasedonanatomicalsiteofdisease
PTB:Refers to a caseof TB involving the lungparenchyma.Miliary TB isclassified as PTB because there are lesions in the lungs. Tuberculousintrathoracic lymphadenopathy (mediastinal and/or hilar) or tuberculouspleural effusion, without radiographic abnormalities in the lungs,constitutes a case of EPTB. A patient with both pulmonary andextrapulmonaryTBshouldbeclassifiedasacaseofPTB.
EPTB:Refers to a caseof TB (definedabove) involvingorgansother thanthe lungs (e.g., pleura, lymphnodes, abdomen, genitourinary tract, skin,joints and bones, meninges). EPTB cases can be either bacteriologicallyconfirmed or clinically diagnosed. Identification of M. tuberculosis (asopposedtohistology)shouldbethebasisofbacteriologicalconfirmationof EPTB. The case definition of an EPTB casewith several sites affecteddependsonthesiterepresentingthemostsevereformofdisease.
Note: Childrenwith only extrapulmonary TB should be classified underthis case definition. Children who have both pulmonary andextrapulmonary TB should be classified under the case definition of
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pulmonaryTB.
For detailed information please refer NTLP manual section 3.4: on TB casedefinitionandc l a s s i f i c a t i o n .Keypoints
• Bacteriologicconfirmationshouldbeattemptedinallchildrenwithpresumptivechildren
• Sputumcanbecollectedbyexpectoration(coughingintoacup),sputuminduction,orgastricaspiration
• CheckfortheclassictetradofTBcontacthistory,signsandsymptoms,positiveTST,andsuggestivelaboratoryandradiographicfindings.
• IntheabsenceofbacteriologicconfirmationtheScoreChartforDiagnosisofTBinChildrenshouldbeusedtomakeaclinicaldiagnosisofTBandreferralfortreatment(Table2.2)
• YoungerchildrenareatgreaterriskfordisseminatedormiliaryTB.
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(4 MANAGEMENTOFTUBERCULOSISDISEASEINCHILDREN
PropermanagementofTBinchildreninvolvesprescribingthecorrectdosesoftherecommended treatment regimen in an appropriate formulation for the rightduration; providing counseling and ancillary care as necessary; managing anyadversereactionsthatarise;andensuringadherenceuntiltreatmentiscompleted.Directlyobserved therapy is the standardof care forTB treatment.Forchildren,theDOTsupervisor canbeaparent/caregiverorhealth careworker.Register allchildrenstartedontreatmentforTBintheunitTBregister.
3.1 Treatmentregimensfortuberculosisdisease
There are two phases to TB treatment: the intensive phase and thecontinuationphase.Duringtheintensivephase,thereisrapidkillingoftheTBbacilli.Mostpatientswithsmear-positiveTBbecomenoninfectiousafterabout2weeksofeffective treatment.During thecontinuationphase, thedrugskilltheremainingbacteria,whichpreventsrelapseaftercompletionoftreatment.
TreatmentofTBdisease inchildren requiresmultidrugcombination therapy.Anti-TBdrugshaveasynergisticeffectoneachother;theircombinedactionsproduceagreatereffectthanthesumoftheindividualmedications.
Ingeneral,paediatric treatment regimensarecomparable toadult regimens.BecauseTB in young children can rapidlydisseminatewith serious sequelae,prompt initiation of therapy is critical. Appropriate regimens, dosing, anddurationareoutlinedinTables3.1and3.2.
Table3.1.RecommendedtreatmentregimensforpaediatricpatientsinTanzania
TBdiseasecategory
Recommendedregimen Intensivephase Continuationphase
AllformsofnewpulmonaryandextrapulmonaryTB*(exceptTBmeningitisandTBofthespine/bones/joints)
2monthsofdailyRHZE 4monthsofdailyRH
TBmeningitis;27ilitaryTB;TBofthespine/bones/joints
2monthsofdailyRHZE 10monthsofdailyRH
PreviouslytreatedTB(relapse,treatmentafterfailure,treatmentafterlosttofollow-up,otherpreviouslytreated)**
3monthsofdailyRHZE*** 5monthsofdailyRHE
MDRTB SeeSection5.2,“Drug-resistanttuberculosisinchildren”
E:ethambutol;H:isoniazid;R:rifampicin;Z:pyrazinamide.
*30 percent of children with a 27ilitary picture on chest radiography have central nervoussystem involvement and should be treated with a 12-month regimen (see a section on“Tuberculousmeningitis”).
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**All previously treated TB cases should be evaluated for MDR TB by sending samples forculture and drug susceptibility testing. Relapse cases are those who have been previouslytreated for TB,weredeclared curedor treatment completed at the endof themost recenttreatmentepisode,andanowdiagnosedwitharecurrentepisodeofTB(eitheratruerelapseoranewepisodeofTBcausedbyre-infection).
Note: If an adolescent is pregnant, refer to the section in the adult guidelines ontreatmentofTBinpregnancy.
Adaptedfrom:GrahamSMetal.Desk-GuideforDiagnosisandManagementofTBinChildren.Paris, France: International Union Against Tuberculosis and Lung Disease; 2010; andDefinitions and reporting framework for tuberculosis – 2013 revision (updated December2014),WHO/HTM/TB/2013.2
3.2 Medicationsanddosages
WhentreatingchildrenwithTB,calculateallanti-TBmedicinedosesbyweightanduseFDCtablets.Itisimportanttoweighthechildateachvisitandadjustmedication dosages as needed. Anti-TB medications, daily dose and range,maximum dose, and potential adverse reactions are provided in Table3.2below. When available, give pyridoxine supplementation to children receiving TBtreatmentataprophylacticdosageof1-2mg/kgperday.
Table3.2.DrugdosingandadversereactionsforthetreatmentofTBinchildren
Drug Daily dose and range mg/kg
Maximum daily dose
Adverse reactions
Isoniazid 10 (7-15) 300 mg Mild hepatic enzyme elevation, hepatitis, peripheral neuritis, hypersensitivity
Rifampicin 15 (10-20) 600 mg Orange discolouration of secretions or urine, vomiting, hepatitis, influenza-like reaction, thrombocytopenia, pruritus
Pyrazinamide 35 (30-40) - Hepatotoxic effects, hyperuricemia, arthralgias, gastrointestinal tract upset
Ethambutol 20 (15-25) - Optic neuritis (usually reversible), decreased red-green colour discrimination, gastrointestinal tract disturbances, hypersensitivity
AdaptedfromWHO,StopTBDepartment.RapidAdvice:TreatmentofTuberculosisinChildren. WHO/HTM/TB/2010.13; and WHO, 2014. Guidance for National TBProgrammesontheManagementofTBinChildren,2ndEdition.
3.3 Fixed-dosecombinationtablets
Use FDC tablets whenever possible to facilitate adherence and simplifyregimens. The FDCs available for use in children in Tanzania includerifampicin,isoniazid,andpyrazinamide(R/H/Z,75/50/150mg)andrifampicinand isoniazid (R/H, 75/50 mg). Children below 25 kg will need to receiveethambutolasaseparatemedication,butolderchildren25kgandabovecanbetreated using adult FDC tablets of rifampicin, isoniazid, pyrazinamide, and
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ethambutol (RHZE, 300/150/400/275mg). Tables 3.3 lists the pediatric FDCdosageneededtoachievethecorrectdosebyweightinchildren<25kg.GuidelinesforusingTBdosingcharts:
• Ifchildislessthan25kg:usepediatricFDCdosingchart(Table3.3)• Ifchildis≥25kg:useadultFDCdosingchart(seeNTLPManual)
Table 3.3. Weight-based dosing of anti-TB drugs for children (0-24.9 kg body weight)
Intensive phase * (2 months)
Continuation phase (4 months)
Weight (kg) RHZ (paediatric) 75/50/150 mg
Ethambutol 100mg
RH (paediatric) 75/50 mg
<4 kg** For infants below 4 kg, consult a pediatric specialist, DTLC, and RTLC for treatment advice
2 - 2.9 kg ½ tablet ½ tablet ½ tablet 3 – 3.9 kg 1 tablet ½ tablet 1 tablet 4 – 7.9 1 tablet 1 tablet 1 tablet 8 - 11.9 kg 2 tablets 2 tablets 2 tablets
12 - 15.9 kg 3 tablets 3 tablets 3 tablets 16 - 24.9 kg 4 tablets 4 tablets 4 tablets ≥25 kg use adult FDCs
H: isoniazid; R: rifampicin; Z: pyrazinamide. *WHO recommends four-drug therapy during the intensive phase for all children.
**For children < 4kg, recommend referral to pediatric specialist/DTLC/RTLC to assist with dosing and treatment in this high-risk group.
3.4 Practical guidance for administering medicines tochildren
PediatricFDCs (RHZandRH)aredispersible in liquidandfruit-flavoredastobemore palatable to children to improve ease of administration for parents andchildren.Inadditiontodissolvinginliquid,thepediatricFDCtabletscanalsobeswallowednormally.
ForpaediatricRHZandRH,adviseparents/caregiversto:• Dissolve the tablets in clean, safe water (approximately 50mL); it will
thenbereadytodrinkafter10seconds• Oncedissolved,itshouldbedrunkwithin10minutes• Entire volume of liquidmust be finished by the child to ensure entire
doseisgiven• Ifthechildspitsuporvomitstheirdoselessthan30minutesafterreceiving
it, re-administer another dose immediately by mixing it with a differentliquid.
• If the child vomits more than 30 minutes after receiving the dose, it hasalreadybeenabsorbedandshouldnotbere-administered
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Forpaediatricethambutol(film-coated),adviseparents/caregiversto:• Attempttohavechildswallowethambutoltabs;ifchildisunabletoswallow,
ethambutolcanbecrushedandmixedwithliquid(butcrushingmayreduceitseffectivenessandpotency)
• Ifthechildspitsuporvomitstheirdoselessthan30minutesafterreceivingit,re-administeranotherdoseimmediately.
• Ifthechildvomitsmorethan30minutesafterreceivingthedose,ithasalreadybeenabsorbedandshouldnotbere-administered
3.5 Steroidusefortuberculosis
Corticosteroidtherapyisgenerallyindicatedasadjuvanttherapywhentreatingchildrenwiththefollowingconditions:• Tuberculous meningitis (steroid use can decrease mortality and long-term
neurologiccomplications).• Severemiliary/disseminatedTB.• Tuberculosispericarditiswitheffusion.• PleuralTBwithmassiveeffusions.• PulmonaryTBwithmediastinallymphglandsobstructingtheairways.
Prescribeoralprednisoloneatadoseof1-2mg/kg/dayupto4mg/kg,withamaximumdosageof60mg/dayfor4to6weeks,followedbyaslowtaperingover 2- 4 weeks (or more) while monitoring for any symptoms ofcorticosteroid withdrawal. Corticosteroid doses may need to be adjustedupward to account for the increased steroid metabolism induced byrifampicin. Treating clinicians should provide necessary information aboutadverseeventstotheirDistrictTuberculosisandLeprosyCoordinator(DTLC).
3.6 Managementofadversereactionstoanti-tuberculosismedications
Ingeneral,apatientwhodevelopsminoradverseeffectsshouldcontinueTBtreatment andbe given symptomatic treatment. If a child develops amajorside effect, stop treatment immediately and urgently refer the patient to ahospitalforfurtherassessmentandtreatment.
SinceFDCsareusedinTanzania,alldrugswillbestoppedatoncewhentheFDC
is discontinued. Contact the DTLC or Regional Tuberculosis and LeprosyCoordinator(RTLC) if singleanti-TBdrugsareneededto treatachild.Table3.4below provides guidelines for management of adverse reactions to anti-TBmedications,basedonsymptoms.
Table3.4.Symptom-basedapproachtomajorandminorreactionstoanti-TBmedications
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Adversereaction(s)
Drug(s)probablyresponsible Management
Major Stop anti-TB drug(s) and refer to a hospital immediately
Skinrashwithorwithoutitching
Isoniazid,rifampicin,pyrazinamide
Stopanti-TBdrugs.
Jaundice(othercausesexcluded),hepatitis,severevomitingorabdominalpain,confusion
Pyrazinamide,isoniazid,rifampicin
Stopanti-TBdrugs.
Visualimpairment(othercausesexcluded)
Ethambutol Stopethambutol.
Shock,purpura,acuterenalfailure
Rifampicin Stopanti-TBdrugs.
Minor Continue anti-TB drugs; check drug dosages Anorexia,nausea,mildabdominalpain
Pyrazinamide,rifampicin,isoniazid
CheckLFTs(ifpossible);ifLFTsabnormalrefertoclinician.Givedrugswithsmallmealsorjustbeforebedtime,andadvicepatienttoswallowpillsslowlywithsmallsipsofwater.Ifsymptomspersistorworsen,orthereisprotractedvomitingoranysignofbleeding,considerthesideeffecttobemajorandrefertoaclinicianimmediately.
Jointpain Pyrazinamide Givenon-steroidalanti-inflammatorydrugorparacetamol.
Burning,numbness,ortinglingsensationinthehandsorfeet(consultpaediatrician)
Isoniazid Givepyridoxine(1-2mg/kg/day),especiallyifHIVpositiveand/ormalnourished.Encouragefoodswithhighamountsofpyridoxine(e.g.potatoes,banana,rice,spinach,nuts,chicken,beef)
Drowsiness Isoniazid Providereassurance.Givedrugsbeforebedtime.
Orange/Redurine Rifampicin Providereassurance.Patientsshouldbetoldwhenstartingtreatmentthatthismayhappenandisnormal.
Adaptedfrom:WorldHealthOrganization,StopTBDepartment.TreatmentofTuberculosisGuidelines:FourthEdition.WHO/HTM/TB/2009.420.
3.7 Managementofcutaeneousreactions
If a patient develops itching without a rash and there is no other obviouscause, prescribe symptomatic treatment with antihistamines and skinmoisturizers.ContinueTBtreatmentwhileobservingthepatientclosely.
Ifaskinrashdevelops(withorwithoutmucosalinvolvement),stopallanti-TBdrugsimmediatelyandrefertothenearesthospitalforfurthermanagement.Once there action has resolved, perform a drug challenge by introducingindividual anti-TBdrugsonebyone, startingwith thedrug least likely toberesponsibleforthereaction(asdescribedbelow)
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Drugchallengeforcutaneousreactions1. Startwithsmalldoses(one-thirdtoone-quarterofthetotaldose)ofthedrug
leastlikely(i.e.ethambutolforcutaneousreactions)toberesponsibleforthereaction.
2. Graduallyincreasethedosetotherecommendeddailydose,over3days.3. Repeattheprocedure,addinginonedrugatatime(nextgiving
pyrazinamide,iftoleratedthenisoniazid,andiftoleratedfinallyrifampicinforcutaneousreactions).
4. Areactionafteraparticulardrugisaddedsuggeststhatthisisthedrugresponsibleforthereaction;andthisdrugshouldnotbeusedagainfortreatment
5. Reactiontoasmallchallengedosewillnotbeassevereastoafulldose.
3.8 Managementofdrug-inducedhepatit is
Many of the first-line anti-TB drugs— pyrazinamide, isoniazid, andrifampicin—can cause liver damage (drug-induced hepatitis). Routinemonitoring of serum liver enzyme levels in asymptomatic children is NOTneeded,butevaluation forsignsandsymptomsofhepatitismustbedoneateachvisitforchildrentakinganti-TB.Assessfor:• Nausea,vomiting,lossofappetite,poorweightgain,darkurine.• Hepatomegaly,jaundice,abdominalpain/tenderness.
Ifapatientdevelopslivertenderness,hepatomegaly,orjaundice,immediatelystopallpotentialhepatotoxicdrugs,obtainserumliverenzymelevels,assessthe child for other causes of hepatitis (other hepatotoxic drugs, viralhepatitis), and refer thechild toahospital for furthermanagement.Furthermanagementshould includeassessing thechild forothercausesofhepatitis(other hepatotoxic drugs, viral hepatitis). Anti-TB drugs should not bereintroduceduntilliverfunctionhasnormalized.
If the patient is severely ill with TB and it is considered unsafe to stop TBtreatment,consultwiththeDTLC/RTLCtoarrangetostartanon-hepatotoxicregimen.
Onceanti-TBtreatmenthasbeenstopped,recheckserumliverenzymes in1to2weeks.ConsultwithyourDTLC/RTLCanddonotrestartanti-TBdrugsuntilserumliverenzymeshaverevertedtonormalandclinicalsymptoms(nausea,abdominal pain) have resolved. If it is not possible to perform serum liverenzymes, it isadvisabletowaitanextra2weeksafterresolutionof jaundiceand upper abdominal tenderness before restarting anti-TB treatment. If thesigns and symptoms do not resolve and the liver disease is severe, a non-hepatotoxicregimen(e.g.ethambutol,streptomycin,andlevofloxacinx18-24months)willbeselectedandinitiatedwithsupportofDTLC/RTLC.
Once drug-induced hepatitis has resolved, perform a drug challenge byreintroducingthedrugsoneatatime.Ifsymptomsrecurorliverfunctiontests(LFTs) become abnormal as the drugs are reintroduced, the last drug addedshouldbestopped. Pleasesee(Annex4)forexamplesofdrugchallengesforanti-TBinducedhepatitisbasedonweightbanddosinginchildren.
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Drugchallengeforhepatitis(tobedonebytheDTLC/RTLC)1. Startwith isoniazid at small doses (one-fourth to one-third of the total
dose),andgradually increasethedoseover3daystotherecommendeddailydose.
2. If no symptoms, next add rifampicin using a rifampicin/isoniazidFDCtablet.
3. If the child can tolerate rifampicin and isoniazid, it is advisable to avoidpyrazinamide. If the patient can tolerate rifampicin and isoniazid andreceived less than 2 months of pyrazinamide, treat withrifampicin/isoniazidforatotaldurationof9months.
4. Ifthechildcannottoleraterifampicinandisoniazid,thenanalternateregimenisrequired(describedbelow)for9to12months.
Alternativeregimensdependonwhichdrugisimplicatedasthecauseofthehepatitis.• If rifampicin can not be used, administer 2months of isoniazid,
ethambutol, and streptomycin, followed by 10months of isoniazid andethambutol.
• Ifisoniazidcannotbeused,6–9monthsofrifampicin,pyrazinamide,andethambutolcanbeconsidered.
If pyrazinamide is discontinued before the patient has completed the intensivephase, the total duration of isoniazid and rifampicin therapy is extended to 9months.
Reintroducing one drug at a time is the optimal approach, but as FDCs arecurrently used in Tanzania, efforts should be made by the health facility toorderandstockadequatequantitiesofanti-TBdrugsthrougheLIMS.
The followingapproach canbeapplied,dependingonwhether thehepatitisoccurredduringtheintensiveorthecontinuationphase:• Whenhepatitisduetopyrazinamideoccursduringtheintensivephaseof
TBtreatment:o Once hepatitis has resolved, restart RH and individual ethambutol.
Send samples for culture and drug susceptibility testing (DST) andmodifytreatmentbasedonresults.Completethe2-monthcourseoftheinitialphase,followedbyrifampicinandisoniazidforthe6-monthcontinuationphase.
• Whenhepatitisoccursduringthecontinuationphase:o Once hepatitis has resolved, re-challenge with isoniazid and
rifampicin,andifnosymptoms,thenrestart isoniazidandrifampicintocompletethe4-monthscontinuationphaseoftherapy.
o If hepatitis or symptoms recur during re-challenge, continue toinvestigate for other causes of hepatitis, and switch to ethambutolandisoniazidtocompletea6-monthcontinuationphaseoftherapy.
3.9 Monitoringtreatmentanddirectlyobservedtherapy
Monitoringpatientsduringanti-TBtreatmentisvitaltoensurepatientsadheretoandcompletetheirtreatmentand/orarecured.SputaMonitoringandFollowUpTestingBacteriologic monitoring using sputum for AFB and culture is needed in
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sputum smear- and culture-positive cases. In these smear-positive cases,obtainsputumforsmearmicroscopy(andculturewhereavailable)attheendofthe intensivephase(secondmonth),attheendofthefifthmonth,andattheendoftreatment.Ifthesputumsmearremainspositiveat2-3monthsoftreatment,conductXpertMTB/RIFwhereavailabletoruleoutdrugresistantTB, or if XpertMTB/RIF is not available, send the specimen for culture andDST.For TB cases that are smear-negative but XpertMTB positive RIF resistancenegative, thesepatientscanbe followedclinicallywithoutneeding to repeatXpertMTB/RIF testingat2monthsandendof treatmentbecauseXpert canremain positive throughout successful treatment. These bacteriologicallyconfirmedTBpatientswill thenhaveanoutcomeof “treatment completed”oncefinishingtheiranti-TBtherapy.In children, XpertMTB/RIF shouldprimarilybeused fordiagnosisof TB, butnot for monitoring of treatment success. However, if the patient is notrespondingwelltoanti-TBtreatmentandthereisconcernoftreatmentfailuredue to MDR-TB, then Xpert MTB/RIF can be repeated in such patients toevaluateforrifampicinresistance.ClinicalMonitoringandFollowUpVisitsEvaluate the child with TB weekly when initiating therapy and every 2 weeksthereafter for the remainder of treatment. Evaluations should include weightmeasurementandareturntotheirgrowthcurve,anassessmentofresponsetotreatment by checking for signs and symptoms displayed by the child beforestarting on TB therapy, adherence to their regimen, and any adverse drugreactions or events. Adjust dosages of medicines as needed as children gainweight.TheentirecourseoftreatmentforchildrenwithTBshouldbeprovidedunderDOTbyahealthcareworkerortrainedtreatmentsupporter(whichcanbeaparentorcaregiver),topreventtheemergenceofdrugresistance.Adherenceisdocumentedonthepatient’streatmentcard.
3.10 Clinicalandbacteriologicresponse
Evaluating clinical response is very important in children with TB becausemanylackbacteriologicconfirmation.
InallchildrenwithTB:• Assessforimprovementorcompleteresolutionofpresentingsymptoms(e.g.,
fever,cough)ateveryfollow-upvisit.• Checkgrowthparameterssuchasweightgainandreturntotheir
growthcurveonamonthlybasis.• Adjustdosingofanti-TBmedicationsasneededasweightchanges.Ifthechildhassmear-negativeTBandisnotimprovingclinicallybytheendoftheintensivephase,refertothenextsection,“Treatmentfailure(confirmingfailureandmanagement).”
Routine follow-up chest radiographs (e.g. monthly) are not indicated, aschildrenoftenhaveaslowradiographicresponse.However,ifthechildisnotclinicallyimprovingonanti-TB,repeatchestx-raysarerecommended.
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In childrenwith smear- or culture-positive TB:Collect a sputum specimen attheendoftheintensivephaseoftreatment.Ifthesmearorcultureattheendoftheintensivephaseisnegative,startthecontinuationphaseoftreatment.Ifthesmearorcultureresultispositive,conductXpertMTB/RIFwhereavailableto rule out drug resistant TB, or if XpertMTB/RIF is not available, send thespecimen for culture and DST andrefer to the next section, on treatmentfailure. Start continuation phase with RHwhile awaiting DST, but ensure closeclinical monitoring of the child while waiting for DST results. If child clinicallydeteriorateswhileawaitingDSTresults,referimmediatelyforMDR-TBtreatment.
3.11 Treatmentfailure(confirmingfailureandmanagement)
A child who is not responding to treatment either by clinical or bacteriologicmeasuresat theendof the intensivephaseshouldbeevaluated forMDRTBbysending a specimen for Xpert MTB/RIF (if available), culture and DST. Thesepatients may have drug-resistant TB, poor treatment adherence, or anothercondition. These children should be referred to secondary/tertiary centres forfurther investigations of MDR TB. If these centres are unable to obtainbacteriologicalconfirmationofMDRTBandthereisahighsuspicionforMDRTB(e.g.childhasknownMDRTBcontact), thechildshouldbereferredtotheMDRTB treatment centre for further evaluation. See Section 5.2, “Drug-resistanttuberculosisinchildren,”forfurtherdetails.
3.12 Managingtreatmentinterruption
Trace patients who miss DOT or an arranged appointment to collect theirmedicines.Contactwithin1day(orassoonaspossible)patientswhomissDOTor a medical appointment during the initiation phase, and contact within aweekthosewhomissDOToramedicalappointmentduringthecontinuationphase. The patient can be traced using the locating information previouslyobtainedand/oravailablecommunityresourcesfortracing. It is importanttofindoutthecauseofthepatient’sabsencesothatappropriateactioncanbetakentopreventfurthertreatmentinterruptions,andtreatmentcancontinuesuccessfully.
Ifachildmisses2to4weeksoftreatment,attempttocollectasputumsamplewhen thechild returns tocare.Collectanothersputumsampleandsend forcultureandDSTifthechildmeetsanyofthefollowingcriteria:• Thechildhaspositivesmear(s)uponreturningtotreatment.• Theinterruptionoccurredintheintensivephase,ratherthanthecontinuation
phase.• Thechildwasrespondingpoorlytotreatmentbeforethe
interruption.• Thereisaknowndrug-resistantTBcontact.
If the child misses 2 to 4 weeks of treatment, continue treatment whilewaitingforsputumresultsandextendtherapybyaddingmisseddoses.Ifthechildmissesmorethan4weeks,thefollowingmustbedone:• SendsputumforcultureandDST.• RestartstandardTBtreatmentwhileawaitingcultureandDSTresults.• RefertoanMDRTBtreatmentcentreifmultidrug-resistantTBisconfirmed.
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3.13 Ancillaryandsupportivecare
IndicationsforhospitalizingchildrenwithtuberculosisAdmit all debilitated, severely ill children with TB to the hospital forstabilisationandnutritional supportaswellas initialdrug therapy.Examplesinclude a comatose child with TB meningitis, an infant withmiliary/disseminatedTB,oranychildwithsevererespiratorydistress.
Youngchildren,especiallyinfants,oftenrequirebriefhospitalizationtoacquirediagnosticspecimenbynasogastricaspirationorsputuminduction.
ManagementoftheasymptomaticneonateexposedtomaternaltuberculosisAny neonate exposed to infectious maternal TB should be screened for TBdisease.Attempttominimizecontactbetweenthemotherandherneonatetobreast feedingperiodsonlyuntil themother startson treatment.Advise themother to continue breastfeeding. Complete separation of the mother andneonateisonlynecessaryifthemotherhaspossibleorconfirmedMDRTB.
ExcludeTB intheneonateaccordingtotheapproachdescribed inSection2,“Diagnosisoftuberculosisdiseaseinchildren.”AllhouseholdmembersshouldalsobeinvestigatedforTB.OnceTBdiseasehasbeenruledout,anyneonatewho was in contact with drug-susceptible TB contact should be started onisoniazid10mg/kgorallyoncedailyfor6months.Theneonateshouldthenbefollowed closely to ensure TB disease does not develop. If TB diseasedevelops, treat the neonate for TB disease. If the infant remainsasymptomatic, complete isoniazid treatment for 6 months and if available,performaTSTatendofIPT.AlsotesttheinfantforHIV.IftheTSTisnegativeornotdoneandHIVstatusisnegative,administertheBCGvaccine2weeksaftercompletingisoniazid.BCGshouldnotbegivenwhile theneonate ison isoniazidbecause it inhibits themultiplicationofBCGorganisms.Closemonitoringoftheexposedneonateisrecommended,especiallyduringthefirstyear.
3.14 Nutritionforchildrenwithtuberculosis
Maintaining good nutrition throughout childhood is important for healthydevelopment.DuringTBtreatment,propernutritionisespeciallyimportanttomaximize immune response and treatment outcome.Malnourished childrenhave impaired immune function with reduced cell-mediated immunity.Furthermore, TB disease worsens malnutrition through catabolism, whichcauses wasting. In a child with LTBI, malnutrition increases the risk ofprogressingfrominfectiontoTBdisease.Failuretothriveandweightlossareimportant clinical features in TB diagnosis in children. Malnutrition is seenfrequentlyinchildrenwithTBinTanzaniaandcontributestopooroutcomes,includingdeath.
Similarly, in HIV-infected children, wasting is associated with increasedmorbidityandpoorsurvival.Onceanti-TBtreatmenthasbeenstarted,ensureadequate nutrition is given in order to counteract the prolonged catabolicstatethatthechildhasexperienced.RefertoAnnex3forDiagnosisandManagementofMalnutrition.
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BreastfeedinginfantsBreastfeeding is recommended forall infants irrespectiveof themother’sTBstatus.Theonlyexception iswhenthemotherhasMDRTB (seeSection5.2,“Drug-resistant tuberculosis in children”). All anti- TB drugs are compatiblewith breastfeeding. The risk of transmission of TB through breast milk isnegligible, and although anti-TB drugs are excreted into breastmilk in smallamounts, there is no evidence that they induce drug resistance. Separationfrom the mother is not advisable where establishment of breast feeding iscritical for child survival. If TB disease is excluded in the infant, the child iseligibleforisoniazidpreventivetreatment(IPT)(seeSection4,“Preventionoftuberculosisinchildren”).
AssessingmalnutritioninchildrenwithtuberculosisPerform a complete assessment of the nutritional status of a childwith TB,includingthefollowing:• Detaileddietaryhistorytoidentifytheexistenceofanyfeedingproblemsand
supportnetworks,includingresourcesavailableathomeforthefamily.• General physical examination to identify features ofmalnutrition, including
taking accurate anthropometric measurements to identify their growthpattern.
Developan individualizednutritional supportplandependingon theseverityof malnutrition and the associated complications. Provide supplemental ortherapeuticfeedingtoallmalnourishedchildrenwithTB.
SeeAnnex3forguidelinesonthemanagementofmalnutritioninchildren.Forfurtherdetails,please refer to recentnationalguidelines formanagementofacute malnutrition in children and community-based management ofmalnutrition.
3.15 Counselingforchildrenwithtuberculosis
CounselinghelpsthechildandfamilycopewiththestressofbeingdiagnosedwithTBandshouldbeanongoingprocess throughoutyourcareof thechildwith TB. TB carries a stigma andmay lead to feelings of shame and fear ofsocialrejection.Thechild’sandparent’s/caregiver’sperceptionsaboutTBmaydiffer from providers’ understanding of the disease process and treatment.BecausemisinformationandmisconceptionsaboutTBincreasethelikelihoodof non-adherence, it is important to identify and address these differencesearly in treatment. It is important to understand the child’s andparent’s/caregiver’sbeliefsaboutTBandtheirconcernsaboutbeingdiagnosedwithTBandaboutTBtreatmentandfollow-upcare.Youshouldclearlyexplainthefollowingtothechildandfamily:• Tuberculosisdisease,itscauseandsymptoms,emphasizingthatTBisa
curabledisease.• ThetreatmentofTBinthechild,including:
o Drugsanddosesthatwillbeprescribed.
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o Treatmentregimenandduration.o Possible side effects of themedications andwhat to dowhen side
effectsoccur.o Importance of taking medications regularly for the full course of
treatment.o Theriskofdevelopingdrug-resistantTBifthechildmissesdoses.o Thatthetreatmentdurationfordrug-resistantTBis2years,thechildhas
tobeadmittedtothehospital,andthereisahighriskofmortality.o OptionsavailableforDOT/treatmentsupport.
• HowtopreventthespreadofTB.• TheimportanceofscreeningfamilymembersforTB.
Asktheparent/caregivertorepeatwhatshe/hehasbeentold.Includechildrenage7andolderinthecounselingsessions.
CounselingabouttuberculosissymptomsCounseltheparent/caregiveraboutcommonTBsymptoms,includingcough,fever,nightsweats,weight loss,andbreathlessness,and that theseshould improveontreatment.Informtheparent/caregiverthatsometimesthechildmightexperiencewheezing due to blockage of the airways by the lymph nodes. Instruct theparent/caregiver to take the child to the hospital immediately if the child haswheezing. Inform parents/caregivers that some children have no symptoms butthatthisisnottypical.
PointstobeconsideredinadherencecounselingIfthereareproblemswithadherence,discussthefollowingwiththechild(atanage-appropriatelevel)andparent/caregiver:• Identifyfactorsaffectingaperson’sadherencetotreatment.• Describestrategiestoenhanceadherence.• Describetherolesofprovider,supporter,andpatientinadherenceto
treatment.CounselingaboutdrugsideeffectsCounselparents/caregiversthatanti-TBdrugsaretypicallyverywelltoleratedinchildrenandadversedrugreactionsareunusual.However,itisimportantthattheyunderstandthepossiblesideeffectssotheycanreportthempromptly should any occur.Provide information to parents/caregivers andtheir children (if age appropriate) about the side effects of each drug beingprescribed.Emphasisetotheparent/caregiverandchildthattheyshouldreturnto care if they experience any adverse reactions. This will allow propermanagement and ensure the least disruption possible to the treatment course.Unexpectedanduntreatedsideeffectscancauseparents/caregiversandchildrento experience unnecessary discomfort or more serious consequences, includingsignificant morbidity or death. Alternatively, uninformed parents/caregivers orchildren may discontinue medicines on their own if they experience sideeffects,whichcanalsoleadtoincreasedmorbidityanddeath.
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PsychosocialsupportStress can alter the immune system and make it less proficient; therefore,offering support to reduce stress in these children is important. Stressmayresultfrommanyfactors,suchasfearofpeerrejectionorbeingdifferent,orbeingconcernedthattheycangiveTBtotheirfriends.• Encourageparents/caregiverstotalkwiththeirchildrentoallow
themtoverbalizeanyfearsandconcernstheymayhave.• Suggestparticipationinasupportgroup.Thiscanallowchildrentodiscuss
theirfearsandconcernswithpeers.• Encourageproperrestandabalanceddiet.• Linkfamiliestosocialassistance.Instructfamiliesnottosegregatechildrenfromotherfamilymembers,asthiscanstigmatiseandaffectchildrenpsychologically
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4 PREVENTIONOFTUBERCULOSISINCHILDREN
4.1 BacilleCalmette-Guérinimmunisation
TheBCGvaccineisaliveattenuatedvaccineandisadministeredaccordingto the Expanded Programme on Immunisation andNTLP guidelines. Thevaccine is effective in protecting against TBmeningitis and other severeformsofTB.However,itisnot100percenteffectiveandsoTBmuststillbeconsideredinBCG-vaccinatedchildrenwithsymptomssuggestiveofTB.
All infants shouldbegivenBCGvaccineatbirth regardlessofHIV status;however, BCG should not be given to HIV-exposed infants who presentwithclearsignsandsymptomsofHIVdiseaseorfull-blownAIDS.
Infantsborntomotherswithtuberculosisdisease
IftheinfantisborntoamotherwithTBdisease,donotgiveBCGvaccine.TheinfantfirstmustbeevaluatedforTBdisease(seeasectionon“Neonataltuberculosis”).IftheneonatehasTBdisease,treat.IfTBdiseaseisruledout,giveIPTforsixmonths.IftheinfantremainsasymptomaticandisHIVnegativeattheendofsixmonthsoftreatment,giveBCGvaccinetwoweeksaftercompletingIPT.DuringthecourseofIPT,theinfantshouldbemonitoredonamonthlybasis.
SideeffectsofBacilleCalmette-GuérinvaccinationCommonandminorsideeffects
Localredness,swelling,andpainoccurinmostinfantsatthesiteofinjectionandmaylastseveralweeks.In1to2percentofvaccinatedinfants,localskininfection may spread to the regional lymph nodes, causing a suppurativelymphadenitis.Somechildrenwithpersistent localizedreactionsmaybenefitfromsurgicalexcision.
Severesideeffects
Asmallnumberofchildrendevelopmoreseverecomplications followingBCGvaccination.Thesemostcommonlyincludelocalabscesses,secondarybacterialinfections,suppurativeadenitis, and localkeloid formation.Mostreactionswillresolveoverafewmonths.
BCG immune reconstitution: Vaccine site abscess formation and/oripsilaterallymphadenitiswithorwithoutsystemicillnessmaydevelopwithinweekstomonthsofinitiationofantiretroviraltherapy(ART)(seeasectionon“ImmuneReconstitutionInflammatorySyndrome,”).
Disseminated BCG: Disseminated BCG is a life-threatening infection thatoccursinasmanyas1percentofHIV-infectedinfantsvaccinatedwithBCG.HIV-infectedorHIV-unknowninfantswhodevelopprolongedfeverorothersystemicsymptomswithinweeksormonthsofBCGimmunisationshouldbeinvestigatedforimmunodeficienciesandtreatedforTBusingthefirst-lineTBregimen,withtheexceptionofpyrazinamide,towhichMycobacteriumbovis
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isresistant.
Key points • BCG vaccine is effective in preventing serious forms of TB in very young
children.• BCG vaccine should be given to infants born to HIV-infected mothersat
birth.• BCG vaccine should be administered to HIV-negative/unexposed infantsand
asymptomaticHIV-exposedinfants.• BCG vaccine should not be given to infants who are confirmed asHIV
infected.• BCG vaccine should not be given to infants born to mothers with activeTB
diseaseuntilinfantscompleteIPT.
Effect of Bacille Calmette-Guérin on tuberculin skin test and interferongammareleaseassay
MostinfantsvaccinatedwithBCGwilldevelopapositiveTSTbutnotapositiveinterferongammareleaseassay(IGRA).
4.2 ManagementoflatentTBinfectioninchildren
Latenttuberculosisinfection(LTBI)isastateofpersistenceimmuneresponseto stimulation byMycobacterium tuberculosis antigens without evidence ofclinicallymanifestedactiveTB.
The lifetime risk of reactivation TB for a person with documented LTBI isestimatedto5-10%withmajoritydevelopingTBdiseaseswithinthefirst fiveyears after initial infection. Children and adolescents havea higher risk thanadultsforprogressiontoTBdisease(withpotentialfordisseminateddisease).MostcasesofprogressiontoTBdiseaseoccurwithin2to12monthsofinitialinfection. IPT has proven to prevent progression of LTBI to TB disease. Thissupports the overall recommendation for the wide use of IPT withincomprehensiveHIVprevention,care,andtreatmentservices.
DiagnosisoflatenttuberculosisinfectioninchildrenTesting for LTBI in children is targeted to specific groups most at risk forprogressingfromLTBItoTBdisease.
TuberculinskintestA TST is performed to diagnose TB exposure. Issues related to dosing,administration, false-positive, and false-negative results in children arediscussedinSection2,“Diagnosisoftuberculosisdiseaseinchildren.”AchildwithapositiveTSTshouldpromptscreeningofallmembersofthehouseholdusingthenationalTBscreeningquestionnaire.ContactscreeningandmanagementNumerousstudieshavefoundthatcontactinvestigationsareavaluablemeansofidentifyingnewTBcases.Youngchildrenlivinginclosecontactwithapersonwith smear-positive pulmonary TB are at particular risk of TB infection and
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disease. The initial steps of the evaluation include taking a history andconductingathoroughphysicalexamination.Itisrecommendedthathouseholdcontactsofasmear-positiveTBcasebescreenedforsignsandsymptomsofTBand IPT given to children without TB disease. Routine assessment of exposedcontactsdoesnotrequireCXRorTST.Thesetestshavelimitationsandareoftennotreadilyavailableorpossible in low-andmiddle-incomesettings. IntheabsenceofTSTorCXR,clinicalassessmentaloneissufficienttodecidewhetherthecontactiswellorsymptomatic.ChildrendiagnosedwithTBdiseaseshouldimmediatelyberegistered for anti-TB treatment under DOT. An algorithm for assessing childhouseholdcontactsofanadultwithsmear-positivepulmonaryTBisprovidedinFigure4.1.
DefinitionsusedincontactscreeningSourcecase:AcaseofpulmonaryTB,usuallysputumsmearpositive,whoisasourceofinfection.
Contactsforscreening:Allchildrenyoungerthan5yearsandchildren5yearsorolderwithsignsandsymptomsofTBwhoareinclosecontactwithasourcecase.
Householdcontact:Livinginthesamehouseholdwiththesourcecase.
Source case investigation for children with TB disease: Many children areinfectedbyhouseholdcontactswithTBdisease,sothecaregiverofanychildidentifiedwithTBshouldbeaskedwhetherthereisanyoneelseinthehousewho has been coughing for more than 2 weeks. If so, these householdcontactsshouldbetoldtocomeintotheclinicforTBscreening.
TBscreeningofsiblings:ThecaregiverofachildwithTBshouldalsobeaskedwhether there are any other children in the home. If so, they should bebrought to the clinic for TB screening and consideration of IPT.A symptomscreenand/orchestx-rayshouldbeusedforTBscreening.
ScreeningforLTBI:LTBIismostlikelytoprogresstoTBdiseaseinveryyoungchildren, so it is important to identify and treat them early. Any householdcontactsofachildwithTBdiseasewhoisyoungerthan5yearsandwhohaveTB disease excluded shouldbe treatedwith daily isoniazid for 6months. AnHIV- infectedchildolder than12monthsshould receive IPT for6monthsaspartofthecomprehensiveHIVcarepackage.
IsoniazidpreventivetreatmentIsoniazid is the regimen of choice for treatment of LTBI amongst childrenexposed to known TB patients. IPT prevents progression of LTBI to activedisease.IsoniaziddosingforLTBIisthesameasfortreatmentofTBdiseaseat10 mg/kg daily (range 7-15 mg/kg daily) for 6 months. Where available,pyridoxinesupplementation(1-2mg/kg/day)shouldbeadministeredtogetherwithisoniazidforpatientswithconditionsthatcanpredisposetoneuropathy,including HIV infection, malnutrition, and diabetes. It should also be
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administeredifthepatientispregnant.
In HIV-infected children exposed to a TB contact, IPT should be givenirrespective of immune status and whether or not the child is on ART.Initiation or completion of IPT should not be the cause of delay in startingART.
GiveIPTtothefollowingchildren:• AllnewbornswithnosymptomsofactiveTBdiseasethatareborntomothers
withactiveTBdisease.• AllHIV-infectedchildrenlessthan12monthswithnosymptoms
ofactiveTBdiseaseandwithaknownTBcontact.• AllHIV-infectedchildrenwhoare12monthsorolderwithnosymptomsof
activeTBdisease.• Allchildrenyoungerthan5yearswithnosymptomsofactiveTBdiseaseand
withaknownTBcontact.Note:LTBItreatmentshouldbeinitiatedonlyafterTBdiseasehasbeenruledout(seeSection2,“Diagnosisoftuberculosisdiseaseinchildren”).
Counsellingforchildrenonisoniazidpreventivetreatment
Explaintothechild(ifageappropriate)andparent/caregiverthattreatmentwiththemedicine isoniazid is essential to prevent the child frombecoming very sickwithTBdisease.Describethepotentialsideeffectsandthattheyshouldreturntotheclinicifanyadversereactionsoccur.
Emphasisetotheparent/caregiverand/orchildthat:• Thefulldurationoftreatmentis6months.• Thechildmustadheretoandcompletetheirtreatment.• The child should return to the clinic if they feel ill whilst on IPT, or if they
developTBsymptomssuchascough,fever,andpoorappetite.• Theparent/caregiverdoesnotneedtolimitthechild’sactivities
inanyway.
Figure4.1.Algorithmforassessingchildhouseholdcontacts
ALGORITHM FOR ASSESSING CHILD HOUSEHOLD CONTACTS
PTB: pulmonary tuberculosis, CXR: chest x-ray, IPT: Isoniazid prophylactic therapy
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CounsellingforchildrenwithlatenttuberculosisinfectionSeeSection3.15,“Counsellingforchildrenwithtuberculosis.”
Adherencetoandmonitoringofisoniazidpreventivetreatment
Ideally, children on LTBI treatment should be monitored by a health careworkertoreinforceadherence,assessforpossibledrugtoxicity,andevaluateforpotentialprogressiontoTBdisease.Monitoringisdoneevery4weeksfortheentiredurationoftreatment.LFTsdonotneedtobemonitoredroutinelyunless the child has underlying liver disease or is taking other potentiallyhepatotoxicmedications.
Isoniazidisusuallywelltolerated,althoughadversereactionssuchasdrug-induced hepatitis, gastrointestinal disturbances, peripheral neuropathy, andskin rashes can occur. The risk for developing isoniazid-induced hepatitis isincreased inthesettingofmalnutrition,pre-existing liverdisease,anduseofotherhepatotoxicdrugs.Underthesecircumstances,baselineliverfunctionassessment should be performed prior to initiation of isoniazid. Thepresentation of hepatotoxicity due to isoniazid is variable. If signs and/orsymptomsofhepatitis(e.g.,nausea/vomiting,poorappetite,abdominalpain,and yellow sclera) are present, isoniazid should be discontinued and LFTsobtained.Usually hepatitis resolves after the discontinuation of isoniazid. Inthiscase,isoniazidshouldnotberestarted.
Rarely,a childwill develop symptomsof TBdiseasewhile taking IPT. In thiscase, the child may have developed breakthrough TB disease. Stop theisoniazid and evaluate the child for TB disease according to Section 2,“Diagnosis of tuberculosis disease in children.” IPT can be resumed if TBdiseaseisruledout.
CompletionofIPTisimportantforgoodindividualandprogrammeoutcomes,butIPTshouldbediscontinuedintherareinstanceofbreakthroughTBdiseaseordrugtoxicity.
SecondaryisoniazidpreventivetreatmentIPTprotectsagainstTBforapproximately2years.Thereafter,theriskofTBre-infection fromnewexposuresgradually returns.Therefore, if there isknownclosecontactofanadultwithinfectiousTB2ormoreyearsafteracompletedcourseofIPT,arepeatIPTcourseisrecommended.
ManagingtreatmentinterruptionIngeneral,6monthsor180dosesofisoniazidshouldbeadministeredforLTBItreatment. Iftheinterruptionis3monthsor less,theremainingdosesshouldbe given and treatment duration extended as needed (upto9months). If theinterruptionismorethan3months,treatmentshouldberestarted.
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4.3 Tuberculosisinfectioncontrol
Contrarytopopularbeliefs,childrenwithTBmaytransmitTBandthereforeinfection control is important, even in health facilities or areas dedicatedonlytothemanagementofchildren.EveryhealthcarefacilitymustdevelopaTBinfectioncontrolplan,whichensuresthatpatientssuspectedofhavingTB are rapidly investigated, appropriately isolated, and rapidly treated topreventTBtransmission.
TheclinicalpresentationofTBinchildrenisvariableandoftenoverlapswiththe presentation of pneumonia, HIV,andmalnutrition, so infection controlmeasures are relevant to all outpatient and inpatient areas with sickchildren.PrinciplesofinfectioncontrolThegoalof infectioncontrol istodetectTBdiseaseearlyandprovideprompttreatment to children to prevent transmission of the disease in the generalcommunity. Health care workers should know priority policies and practicesaddressing infection prevention control in both children and adults. Theseinclude administrative, environmental, and respiratory controlmeasures. ThedetailsarefoundintheNationalGuidelinesforTuberculosisInfectionControl.
Keypoints• GiveIPT,onceactiveTBdiseaseisruledout,to:
o Childrenyoungerthan5yearswithknownactiveTBcontacts.
o HIV-infectedchildrenmorethan12monthsofage.o HIV-infectedchildrenlessthan12monthswithknownactive
TBcontacts.• ChildrenwithpresumptiveTBshouldbereferredforinvestigationof
TB.• TreatLTBIinchildrenwith6monthsofisoniazid(IPT).• IsoniazidpreventivetreatmentprotectsagainstTBforabout2
years.
Keypointsspecificforchildren• ChildrencantransmitTBinfectiontoothers,especiallytothose
withHIV/AIDSandwithmalnutrition.• ChildrenwithpresumptiveorconfirmedTBshouldbecaredforina
separate,well-ventilatedroom,awayfromHIV-infectedchildren.• InfantsborntomotherswithMDRTBshouldbeseparatedatthe
earliestopportunitytominimizeriskofcontractingtheinfection.
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5 PAEDIATRICTUBERCULOSISINSPECIALSITUATIONS
5.1 TB/HIVinchildren
ThecomplexinteractionsbetweenTBandHIVrequirehealthcareworkerstobeknowledgeableabout themanagementofpatientswithbothTBandHIV.The available evidences indicate that TB has a significant adverse effect onoutcomesinHIV-infectedchildren.
DiagnosingHIVinchildrendiagnosedwithtuberculosisdisease
PerformHIVtestingonallchildrenwhoarepresumptiveTBordiagnosedTBcases.ChildrenfoundtobeHIVinfectedshouldbereferredtoHIVcareandtreatmentfacilitiesforfurthermanagement.RefertothenationalHIVguidelinesforfurtherdetailsonHIVtestingproceduresandmanagementofHIVinfectioninchildren(seeAnnex4formoreinformationonHIVtestingofchildrenyoungerthan18months).
DiagnosingtuberculosisdiseaseinchildrenwithHIVScreen all HIV-infected children for TB disease at the time of their HIVdiagnosis and at every visit to an HIV care and treatment clinic, using thenationalTBscreeningquestionnaire (refer toAnnex6).Diagnosisofchildrenwhoscreenpositive forTBshould followthenormalprotocol fordiagnosingTBinchildrenasdescribedinSection2,“Diagnosisoftuberculosisdiseaseinchildren.”
Since the most common means of transmission of HIV in children is frommothertochild,thepeakageprevalenceforHIVislessthan5yearsold.ThisisalsothemostdifficultagegroupinwhichtoconfirmadiagnosisofTB.
Diagnosing TB in HIV-infected children is further complicated by thefollowing:• AnoverlapofclinicalandradiologicalfindingsofpulmonaryTBandthatof
otherformsofHIV-relatedlungdiseases.• HIV-infectedchildrenwithTBdiseaseoftenhavefewerTBbacteriathannon-
HIV-infectedchildren,furtherincreasingthelikelihoodofnegativesputumsmearresults.
• ExtrapulmonaryTBanddisseminateddiseasearemorecommoninHIV-infectedchildren.
• DifficultyinterpretingtheusualdiagnostictoolsbecausetheyarelessspecificinHIV-infectedchildren(seeAnnex7)forasummaryoftheimpactofHIVonTBdiagnostictestinterpretation).
• SignsandsymptomsofTBarelessspecificinchildrenwithHIVbecausesymptomsofTBcanoverlapwithsymptomsofHIV(seeAnnex8)forcommoncausesoflungdiseasesinHIV-infectedinfantsandchildren).
ClinicalpresentationofTB/HIVinchildrenAsinadults,thenaturalhistoryofTBinachildinfectedwithHIVdependson
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the stage of HIV disease. Before HIV infection advances and the child’simmunity isgood, thesignsofTBare similar to those inachildwithoutHIVinfection.However,infantshaveimmature immunesystemssotheir immunestatus is already somewhat compromised. As HIV disease progresses andimmunity declines, dissemination of TB becomes more common and TBmeningitis,miliaryTB,andwidespreadTBlymphadenopathycanoccur.
TreatmentoftuberculosisdiseaseinHIV-infectedchildren
Compared toHIV-uninfected childrenwith TB,HIV-infected childrenwith TBhaveworse outcomes of TB treatment and higher rates ofmortality. This islikelyduetoacombinationof factors, includingsevere immunesuppression,co-existing malnutrition, HIV-related co-infections, Immune ReconstitutionInflammatorySyndrome,andgreaterproblemswithadherencetotreatment.The majority of deaths in HIV-infected children receiving treatment for TBoccurinthefirst2months(intensivephase)ofTBtreatment.
Importanttreatmentissuestoconsider:• StartTBtreatmentfirstforallHIV-infectedchildrenwithTBdiseaseandwho
arenotyetonART.• Prescribe the same dosages and regimens of anti-TB treatment to HIV-
infectedchildrenwithTBdiseaseasareusedinHIV-uninfectedchildren.• StartARTassoonaspossibleinallHIV-infectedchildrenwithTBregardlessof
CD4levelsonceTBtreatmentistoleratedideallywithinthefirst2to8weeksofstartingTBtreatment.
• Monitortreatmentandconductfollow-upinacareandtreatmentclinic(CTC)andaTBclinic,respectively,aspernationalrecommendations(refertoSection3,“Managementoftuberculosisdiseaseinchildren,”fordetailson TB follow-up, and refer to nationalHIV guidelines for details onHIVfollow-up).
• OnceTBdiseasehasbeenexcluded,evaluateallHIV-infectedchildrenforIPT(refer to Section 4, “Prevention of tuberculosis in children,” for furtherdetails).
SimultaneoustreatmentofbothtuberculosisdiseaseandHIVinchildren
AllHIV-infected childrenwithTBdisease fulfill criteria for initiation ofARTregardlessof theirCD4 levels,as per national guidelines. ARTwill reducemortality in HIV-infected children with TB and the risk of recurrent TBfollowing completion of anti-TB treatment. ART decreases the risk ofdeveloping TB disease in HIV-infected children who are TB exposed andinfected. HIV-infected children with LTBI are candidates for IPT (refer toSection4,“Preventionoftuberculosisinchildren,”fordetails).
ChildrenwithTBandHIVwhoarereceivingbothARTandanti-TBtreatmentneed special consideration because of the potential drug-drug interactionsbetween rifampicin and non-nucleoside reverse transcriptase inhibitors(NNRTIs)andproteaseinhibitors,thehighpillburden,adherenceconcerns,andanincreasedlikelihoodofdrugtoxicity.RifampicinreducesdruglevelsofNNRTIs andprotease inhibitorswhen they are co-administered. This can
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lead to sub-therapeutic ART drug levels and thereby increase the risk fordevelopingARTdrugresistanceandARTtreatmentfailure.
BelowareregimensrecommendedforuseinchildrenwithTB/HIV.Efavirenzis thepreferredNNRTI tobeused concurrentlywith rifampicin; however, itcanonlybeusedinchildrenolderthan3yearsandweighingmorethan10kg.Nevirapineandlopinavir/ritonavir(LPV/r)shouldbeavoidedwhenthechildistaking rifampicin because the levels of nevirapine and LPV/r will decreasesignificantly,whichcancompromisevirologicsuppression.
RecommendedARTRegimensforChildrenReceivingStandardTBTreatment
Forchildren<3yearsofageonAnti-TB–• If on NVP based regimen, continue NVP ensuring that dose is 200mg/m2
(optimized dose), if on LPV/r based regimen double the dose of LPV/r
Forchildren>3yearsofage-ABC/3TC+EFV
• Itisrecommendedtogive2NRTIswithEFVandifonLPV/rbasedregimendoublethedoseofLPV/r Key: ABC: abacavir; AZT: zidovudine, 3TC:Lamivudine,EFV: efavirenz, NRTI:nuclosidereversetranscriptaseinhibitor,,LPVr:Lopinavir/Ritonavir
Whentostartantiretroviralsininfantsandchildrenreceivingstandardanti-tuberculosistreatment
Earlier ART treatment is associated with better outcomes. Children withTB/HIVnotyetonARTwhohavebeeninitiatedonanti-TBtreatmentshouldbe started on ART as soon as they are tolerating their anti-TB medicines.ideallywithin2weeksafterthestartofanti-TBanddefinitelyby8weeks.
MonitoringduringtherapyandmanagementofadversereactionsInfantsandchildreningeneraltolerateanti-TBtreatmentconsiderablybetterthanadults.Thebiggest therapeuticchallenge is thepotential fordrug-druginteractionsbetweenanti-TBmedicinesandART,andachievingproperdruglevels. Ingeneral,additional laboratorymonitoringofLFTs isnotrequired inchildren with TB/HIV unless there are signs and symptoms of liver toxicity(refer to Section 3, “Management of tuberculosis disease in children,” forfurther details). Table 5.1 presents overlapping side effects of anti-TBtreatmentandantiretroviralmedications.
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Table5.1.Overlappingsideeffectsofanti-TBtreatmentandantiretroviralmedications*
SideeffectPossiblecauses
Anti-TBdrugs Antiretroviraldrugs
Peripheralneuropathy Isoniazid,cycloserine None
SkinrashRifampicin, isoniazid,pyrazinamide,cycloserine
Nevirapine, efavirenz,abacavir
Gastrointestinalsymptoms All All
HepatitisPyrazinamide, rifampicin,isoniazid,ethionamide
Nevirapine, proteaseinhibitors
Anaemia Rifampicin Zidovudine
*Formanagementofadversereactions,refertoSection3,“Managementoftuberculosisdiseaseinchildren.”
ImmuneReconstitutionInflammatorySyndromeImmune Reconstitution Inflammatory Syndrome (IRIS) is an inflammatoryprocess characterized by transient worsening of clinical disease followinginitiationof treatmentdue to restorationof thebody’s capacity tomount aninflammatoryimmuneresponse.ThisconditionmayarisewhenARTisinitiatedinapatientwithvery lowCD4levelsand/orahighviral load.Onset isusuallywithinthefirst3monthsafterstartingART.IRISdevelopsin5to20percentofchildrenstartingART.
When IRIS occurs, it is commonly associated with TB (current orundiagnosed) or recent BCG vaccine. Risk factors for TB IRIS include lowbaselineCD4count,extensiveTBdisease,earlyinitiationofART,andrapidimmunologicalandvirologicresponsestoART.Typically,apatientwhowasdoingwell and responding to therapy suddenly getsmuchworse or hasnew symptoms or signs; hence, this is also referred to as a paradoxicalreaction. In addition, sometimes ART start alone can unmask priorquiescentTB,soa fewmonthsafterstartingART,signsandsymptomsofTBappear.SymptomsofTBIRISincludeworseningTBsymptomsandchestx-rayfeatures,new and persistent fevers after starting ART, and evidence of local and/orsystemic infection or inflammation (e.g., enlarging lymph nodes and thedevelopment of fistulae and cold abscesses or worsening central nervoussystemdiseaseduetoenlargingcerebraltuberculosis).
WhenIRISisdetected,thefollowingactionsshouldbetaken:• RuleoutTB/HIVtreatmentfailure,sideeffectsofTBandHIVtreatment,and
pre-existinguntreatedopportunisticinfections.• Continue both ART and anti-TB treatment unless severe toxicity is
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suspectedorconfirmed(e.g.,elevatedLFTs).• Inseverecases,giveprednisoloneatadoseof1-2mg/kgfor1to2weeks;and
thereafter,graduallydecreasethedose.• Provideothersupportivemeasuresaswarranted.
AppropriateuseofcotrimoxazolepreventivetherapyCotrimoxazole preventive therapy (CPT) is a safe and cost-effective strategyandshouldbeuniversallyadministeredtoallHIV-infectedinfantsandchildrenwho do not have prior contraindication to its use. CPT prevents severalsecondary bacterial, fungal, and parasitic opportunistic infections, andsignificantly reduces morbidity and hospitalization from opportunisticinfections.
ProvideCPT to all childrenwith TB/HIV,and toHIV-exposed infants if notalreadygivenaspernationalHIVguidelines.Cotrimoxazoleisprovidedataprophylactic dose of 4 mg/kg of trimethoprim once daily. In Tanzania,cotrimoxazole is available in a combination tablet of trimethoprim80mg/sulfamethoxazole400mgandasasyrupinthesameratio,containing40mg trimethoprim/200 mg sulfamethoxazole per 5 ml (see Table 5.2 forrecommendeddosagesbyweight).
Table5.2.RecommendeddosesofcotrimoxazolebyageAgerange Trimethoprim/Sulfamethoxazole(TMP/SMZ)(Septrin®,Bactrim®)
4mg/kgoncedaily(forprophylaxisagainstopportunisticillnesses;higherdoseswillberequiredfortreatment)
Syrup:40mg/200mg/5ml
Single-strengthtablet:80TMP/400SMZ Birthto6months 2.5ml ¼tablet 6months-5years 5ml ½tablet 5years-14years 10ml 1tablet ≥14years 2tablets
HIVcounselling(provider-initiatedtestingandcounselling)Tell theparent/caregiver (orchilddependingonage)thatabout36%ofTBpatientshaveHIV,thenadviceHIVtestingforthechildandparents.Also informtheparentsthatbyknowingHIVserostatusearlier,prompttreatmentandbetteroutcomesarepossible.ObtainHIVtestatTBclinicorrefertoRCHifearlyinfantdiagnosisisneeded.
Treatmentadherencetoanti-tuberculosisandantiretroviralmedications
Informparents/caregiversandchildrenthat:• Byadheringtotreatment,apatientcanmanageHIV,cureTB,andprevent
thedevelopmentofresistance,therebyimprovingtheiroverallhealthandprotectingthehealthoftheircommunity.
• TuberculosistreatmentislongbutwillcuretheirTBandcanhelppreventothersfromgettingsickwithTB.
• HIVtreatmentislifelongthatcankeepthemhealthyaswellaspreventthetransmissionofHIVtoothers.
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Giveenoughage-appropriateinformationtothechildtoensureadherencetoTB/HIV treatment. Counseling is an ongoing and lifelong activity, so moreinformation and support must be provided as children mature. Help theparent/caregiver become a knowledgeable adviser and advocate for theirchildren, and be sure to review the following with the patient andparent/caregiver:
• TBandHIVtransmission
• Clinicalcareandtreatment
• Goodnutrition,exercise,hygiene,andrest
• Psychosocialcare
AdherencetotreatmentmanagesHIV,curesTB,andpreventsresistance,thusimprovingthechild’shealthandprotectingothers
DisclosureofTB/HIVstatustothechildThemostimportantcounsellingmomentforchildrenwithTB/HIVisdisclosureoftheirTBandHIVstatus.Beawarethatparents/caregiversandchildrenmayhavestrong emotions at this time, particularly when the child’s HIV infection is theresult of mother-to-child transmission. Very often, parents are terrified of theidea of telling their child that they have TB and HIV and that the parent(s)has/havepartlycontributedtoit.Parents/Caregiversoftendonotknowwheretobegin,orhowtodealwiththeirchild’sself-isolation,sorrow,andwithdrawalthat may follow after the disclosure.Many parents feel tremendous guilt andshame,andworrythattheirchildwillbecomeangryorrejectthem.Discusstheseissueswithparents/caregiversbeforedisclosuretothechildisundertaken.Betteroutcomesareachievedwhenadisclosureprocesstargetsbothchildrenandtheir parents/caregivers and when both parties are included in primarycounselling fromthebeginningof thedisclosureprocess.Sharingofexperiencesfrom other parents—ideally by providing a parent support group—can behelpful to reassureparents/ caregivers thatwhile their child may be initiallyangry and upset, theymay also feel great relief at finally knowing the truth.Havingtheinformationwillallowthemtoaddressthesefeelings,withthegoalofbeing able to come to an acceptance of their diagnosis.While the best age atwhich todisclosedependsverymuchon the individual child, ingeneral, school-agedchildrencanhandleage-appropriateinformationaboutTBandHIV.Makingsurethatparents/caregiversarewellpreparedandsupportedthroughoutthe disclosure process will ensure a successful disclosure process that will notnegatively affect the child’s clinical and psychosocial well-being and therelationshipwiththeirparent/caregiver.
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5.2 Drug-resistanttuberculosisinchildren
Drug-resistantTBisdefinedasTBcausedbyastrainthatisresistanttooneormoreanti-TBmedicines.Thismaybegroupedinto:• Mono-resistant TB: Resistance to a single drug,most commonly isoniazid.
Thispatternofresistanceisnotusuallyassociatedwithaworseoutcomeanddoesnotrequiremodificationofthetreatmentregimen,aslongasthereare4 drugs in the initial phase and rifampicin is included throughout the fulldurationoftreatment.Rifampicinmono-resistanceoccurs,butisuncommonandisseenmainlyinpatientswithHIVinfection.
• Poly-resistant TB: Resistance to more than one drug, but not thecombinationofisoniazidandrifampicin.
• MDR-TB: Resistance toat least isoniazid and rifampicin.MDRhas amajoradverse effect on treatment outcome, and infected patients will generallyrequiretreatmentwithsecond-lineregimens.
• RR-TB: Resistance to rifampicin detected using molecular tests or culture(phenotypicorgenotypicmethods),withorwithoutresistancetootheranti-TB drugs. It includes any resistance to rifampicin, in the form ofmonoresistance,multidrugresistance,polydrugresistance,orextensivedrugresistance.
• XDR-TB: MDR-TB, plus resistance to fluoroquinolones, and at least 1 of 3injectable agents (amikacin, kanamycin, capreomycin). XDR-TB cases areoften also resistant to all 4 first-line agents, making patients significantlymoredifficulttotreat.
• Primarydrug-resistance: “NewCases”:Drugresistance inapatientwhohasneverbeentreatedforTB,orreceivedlessthan1monthofTBtherapy.Drug-resistant TB in children is usually primary and due to contact with aninfectiousadultcase.
• Acquired drug-resistance:“Previously Treated Cases”: Drug resistance in apatientwhohasreceivedatleastonemonthofanti-TBtherapy
Key points • When TB and HIV interact, they intensify and worsen each other. • If a child has HIV infection, they need to be screened for TB, and ifachild
hasTB,theyneedtobetestedforHIV.• Start ART as soon as possible in all HIV-infected children with TB
regardless of CD4 levels once TB treatment is tolerated ideally within the first 2 to 8weeks of starting TB treatment.
• Immune Reconstitution Inflammatory Syndrome is not treatment failurebuta recovery of the immune system and exaggerated presentation of unmaskedinfection.
• Continue anti-TB medicines and ART when HIV-infected children developIRIS,unlessseveretoxicityoccurs.
• Cotrimoxazole preventive therapy is universally recommended for HIV-infectedchildren.
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Multidrug-resistant tuberculosis (MDR-TB) is defined as resistance to bothisoniazidandrifampicinwithorwithoutresistancetootherfirst-lineanti-TBdrugs (streptomycin, pyrazinamide, andethambutol). In adults, MDR TB ismore common in previously treated TB cases (acquired drug resistance);however,inchildren,MDRTBisusuallytheresultofdirecttransmissionofM.tuberculosis-resistant strains (primary drug resistance) from an adultsickperson.
Diagnosisofmultidrug-resistanttuberculosisinchildrenChildren usually have paucibacillary or extrapulmonary TB disease,furthermore, sputum samplesmay be difficult to obtain in younger childrenand bacteriologically confirmation of drug resistant TB diagnosis may bedifficulttoobtain.In view of these gaps, a high index of clinical suspicion is needed whendiagnosingMDRTBinchildrenandthefollowingwillbeinvestigatedforMDRTB:• AchildwhoisaclosecontactofaninfectiousMDRTBcaseincludinghouseor
schoolcontact.• AchildwhoisaclosecontactofaTBpatient,whohasfailedtreatment,was
losttofollowupordiedduringtreatment.• Failure to improve clinically after 2-3 months of first-line TB treatment,
includingpersistenceofpositivesmearsorcultures,persistenceofsymptoms,andfailuretogainweight
• AchildwithprovenTBwhoisstillbacteriologicallypositiveafterfivemonthsof appropriate treatment with first-line anti-TB medications (treatmentfailure).
• Historyofprevioustreatmentwithinthepast6-12months
Despite the diagnostic challenges, every efforts should be made to obtainspecimensfromallpossiblesources,likegastricaspiration,sputuminduction,or lymphnodeaspiration for bacteriologic confirmationof drug resistant TBthrough Xpert/MTB/Rif or culture and DST or Line Probe Assay (LPA) tests,becauseDRTBisamicrobiologicaldiagnosiseveninchildren.Cultureresultscan be available within two weeks (Liquid Media), and DST results areavailableafteratleast6weeks.XpertMTB/Rifisarapidmoleculartestandtheresultscanbeobtainedin3hours’time.ThediagnosisofDRTBinchildrenismade by a review panel of experts on DR TB based on history, physicalexamination, and laboratory findings. ChildrendiagnosedwithDRTB shouldbe reported to the DTLC for recording and referred to a DR TB treatmentcentreforfurthermanagementasstipulatedintheOperationalGuidelinesfortheManagementofDrug-ResistantTBinTanzania.
PretreatmentscreeningandevaluationBefore referral for DR TB treatment, the following interventions should beperformed:• Inform the parent/caregiver and family about DR TB, its treatment and
duration.• Evaluate nutritional status, and inform the mother on proper feeding
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practicesandmaintenanceofafeedingchart.• CounselandtestforHIV,ifHIVstatusisunknown.• Ensurethechildhasabaselinechestradiograph.
The MoHCDGEC recommends using a standardized treatment regimenapproachforall identifiedpaediatricDRTBcases,sothatallpatientsreceivethesameregimen.Childrenshouldbemanagedunderthesameprinciplesasadults,thedurationoftherapyforstandardizedtreatmentregimenofDRTBinchildren is20to24.All treatmentshouldbegivendailyandunder facilityDOT.Treatmentconsistsoftwophases:• Intensive phase, in which the child takes at least four effective drugs,
includinganinjectable,for8months.PediatricMDRTBpatientsshouldonlybehospitalizedwhentheyhaveotherco-morbidconditions*associatedwithMDR TB and/or have under nutrition so as to receive nutritional care andtreatment. These patients should be transferred to the community forcontinuation of treatment once they reach the early discharge criteria (asearly as two weeks after initiating treatment). Majority of patients notmeetingabovecriteriashouldbeinitiatedtreatmentonanoutpatientbasisintheircommunities.
• Continuationphase, inwhichthechildtakesthesamedrugsexceptfortheinjectableatahealthfacilityclosetotheirhomeforatotalof12months.
*Common co-morbid conditions seen in children with MDR-TB include; HIV,diabetesmellitus,orthopedicproblems,andreactiveairwaydisease.
Tables 5.3 below provides a list of the drugs for each treatment phase, andTable5.4providesdetailsonpaediatricdosagesforsecond-lineanti-TBdrugs.
Table5.3.StandardizedMDRTBmedicinesanddurationoftreatmentregimenTreatmentphase Drugs Duration
Intensivephase AmikacinorkanamycinOfloxacinorlevofloxacinPyrazinamideEthionamideCycloserineEthambutol
8months
Continuationphase LevofloxacinEthionamidePyrazinamideCycloserineEthambutol
12 months
Table5.4.Paediatricdosingandadversereactionofsecond-lineanti-TBdrugs
Drug Dailydose(mg/kg)
Frequency Maximumdailydose
Adversereactions
Amikacin 15-22.5 Oncedaily,5timesaweek
1g Ototoxicity,nephrotoxicity
Kanamycin 15-30 Oncedaily 1g Ototoxicity,nephrotoxicity Capreomycin 15-30 Oncedaily 1g Ototoxicity,nephrotoxicity Moxifloxacin 7.5-10 Onceaday 400mg Arthropathy,arthritis Levofloxacin
ⱡ 7.5-10 Onceaday 750mg Arthropathy,arthritis Ethionamide 15-20 Twiceaday 1g Vomiting,gastrointestinalupset
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Cycloserine 10-20 Onceortwiceaday
1g Centralnervoussystemmanifestations(psychosis,depression),neurological
PAS 200-300 Twiceorthricedaily
12g Vomiting,gastrointestinalupset
Pyrazinamide* 30-40 Oncedaily 2g Hepatotoxicity,hyperuricemia,arthralgias,gastrointestinalupset
Ethambutol* 15-25 Oncedaily 2.5g Opticneuritis(usuallyreversible),decreasedred-greencolourdiscrimination,gastrointestinalupset,hypersensitivity
PAS:para-aminosalicylicacid.*First-lineanti-TBdrugs.ⱡLevofloxacin is dosed twice daily for children 5 years of age and under (total daily dose: 15-20mg/kg/day)andoncedailyforchildrenover5yearsofage(totaldailydose:7.5-10mg/kg/day).This isdonebecausechildrenunderfivemetabolizethelevofloxacinfasterthanthoseolderthanfive.(Source:ManagementofDrug-ResistantTuberculosisinChildren:AFieldGuide.Boston,USA:TheSentinelProjectforPediatricDrug-ResistantTuberculosis;November2012)
Adverseeffectsofsecond-lineanti-tuberculosisdrugsinchildrenChildren generally tolerate second-line medicines well, with adverse eventsoccurring less frequently than inadults. Caregivers shouldbemadeawareofpossible adverse events and told to immediately report any possible adverseevent.No second-lineanti-TBdrugsareabsolutely contraindicated in childrenunless hypersensitivity or an intractable adverse reaction has beendocumented.
MonitoringofchildrenonMDRtreatmentChildreninthecontinuationphaseofMDRTBtreatmentshouldbemonitoredforsimpleadverseeffectswithsupportfromtheDTLC,asshowninthetablebelow.
Table5.5.TreatmentmonitoringofchildrenwithMDRTB
Parameter Frequency Fever,cough,andlossofappetite Monitordaily. Sputumforsmear,culture Monthly. Weight Dailyinhospital,monthlyinthecontinuationphase. Height Monthly. Fullbloodpicture Baselineandquarterly. Creatinine Twicemonthlyforthefirstmonth,thenmonthlyinthe
intensivephaseandinthecontinuationphaseifindicated.
Potassium Monthly.Iflow,obtaincalciumandmagnesium. AST,ALT,totalbilirubin Monthly. TSH Baseline,thenquarterly. Audiometryandvestibularfunction Monthlyintheintensivephasethenquarterly X-rayinvestigation Atbaseline,every6months,andatendoftherapy
ALT:alanineaminotransferase;AST:aspartateaminotransferase;TSH:thyroid-stimulatinghormone.
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MonitoringtreatmentefficacyObtainasputumspecimenforsmear,culture,andDSTmonthlyuntilthechild’ssputumconvertstosmearandculturenegative.Sputumconversion isdefinedas two consecutive negative smears and cultures taken 30 days apart. Afterconversion,obtainsmearsatleastmonthlyandculturesevery2months.
Inchildrenwhoarenotculturepositiveinitially,treatmentefficacyorfailureisdifficult to assess. Always monitor weight carefully in children to adjustdosagesasthechildgainsweight.Thefollowingarethefirst(oronly)signsoftreatmentfailure• Failuretogainweightadequately;or• Failuretothrive;or• Weightloss.
TheshortMDRTBRegimen
Currently, the Ministry is in the process of introducing short term DR-TBtreatmentregimenwhichwillshortenthedurationoftreatmentfrom18to24monthsdownto9to11months.
The regimen is endorsed by WHO and comprises of the following drugcombinations;
4-6Km,Mfx,Pto,Cfz,z,Hhighdose,E/5Mfx,Cfz,z,E
[i.eKm=Kanamycin,MfX=Moxifloxacin,Pto=Prothionamide,Cfz=Clofazimine,z=Pyrazinamide,H=Isoniazid,E=Ethambutol]
The intensive phase: This will be given daily for four months. The Kanamycin,clofazimine, Moxifloxacin, ethambutol, high dose isoniazid, pyrazinamide andprothionamide will be extended until smear and/or culture conversion if smearconversion is not achieved within four months, with a maximum of 6 months.Kanamycin will be given thrice-weekly from the fourth month onwards. Failuremight be declared at 6 months for those who have both positive smear at 6monthsandpoorclinicalresponsetotreatment.
Thecontinuationphase:Moxifloxacin,ethambutol,pyrazinamideandclofaziminegivendailyforafurtherfivemonths.
Therecommendeddosagebyweight,can be used inpeople living with HIV,includingthosewhoarereceivingantiretroviraltreatmentandinchildrenunder15years.Howevertheregimenisnotrecommendedinpatientswithresistancetoanyofthetwodrugclasses(Pre-XDR;FQs,secondline injectables(SLinj))orwhohaveextensivelydrug-resistantTB(XDR-TB;MDR-TBplusadditionalresistancetoafluoroquinoloneandasecond-line injectable).TheshortMDRTBregimenshouldbeprovidedinaccordancewithexistingNationalMDRTBguidelines.
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Screening of children in contact with multidrug-resistant tuberculosispatients
Closecontactsofdrug-resistantTBpatientswhodevelopTBdiseaseusuallyhavedrug-resistantdiseasewiththesameresistancepattern.Allchildrenwhoare contacts of an infectiousMDR TB case should be screened forMDR TBdisease. Screening should be done even in asymptomatic children, andinclude:• Takingahistory.• Physicalexamination.• Laboratoryfindings(sputumforsmearandculture,andx-rayinvestigations).• HIVcounselingandtestingifnotyetdone.
ChemoprophylaxisCurrently, there areno recommendations for chemoprophylaxis forMDRTBcontactsinTanzania.ThealternativetochemoprophylaxisinMDRTBcontactsis careful clinical follow-up, every 2 to 3months for the first 6months, andthereafter,every6monthsforatleast2years.Ifactivediseasedevelops,referforMDRTBtreatment.
Management of a newborn child of a mother with multidrug-resistanttuberculosisAnewbornshouldbeseparatedfromamotherwithuntreatedMDRTBorwhoisstill smear/culture positive despite treatment. Once a mother is no longercontagious (smear/culturenegative), the infantmaybecared forby themother(separationisnolongerneeded).Advisethemothertoconsiderusingbreastmilksubstitutes to avoid possible adverse effects, because most second-line TBmedicationsareexcretedinbreastmilk.
OncethemotherisnolongerinfectiousbutstillintheintensivephaseoftreatmentattheMDRTBcentre,familymembersmaybringtheinfantforvisits,whichshouldoccuroutdoors.
Key points • Most children are culture negative, making the diagnosis of drug- resistantTB
difficult.• All children who are contacts of an infectious MDRTB case shouldbe
screenedforMDRTBdisease.• Standardized treatment regimen of Multidrug-resistant tuberculosis requires
18 to 24 months of appropriate treatment (in two phases: intensive andcontinuation
• Short Multidrug-resistant treatment regimen of tuberculosis requires 9 to 11 months of appropriatetreatment(intwophases:intensiveandcontinuation.
• Always monitor weight carefully in children to adjust doses as thechildgainsweight.
• Close and extensive monitoring is required for all patients receivingtreatmentwithsecond-lineanti-TBmedicines.
• No chemoprophylaxis is indicated for children who are MDR TBcontacts.• Mothers with MDRTB are able to provide care for their newborns once
theyarenolongerinfectious(smearsandculturesarenegative).
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6 RECORDING,REPORTINGANDUSEOFDATAFORCHILDRENWITHTUBERCULOSIS
6.1 Introduction
Reliableandcompletedataintherecordingandreportingsystemareessentialformonitoring patient outcomes andprogrammeperformance. ChildrenwithTB should always be included in the routine recording and reporting system.Thedata collectedatany level shouldbeanalysedand interpreted locally forreporting,planning,monitoringpurposes,makingevidencebaseddecisionsandaccountability.DefinitionsRecording - capturing data on patient management over time and across clinicalsites.Informationiswrittendirectlyonpaperformsorenteredintoacomputer.
Reporting - routine tracking (monitoring) of priority program managementinformation of summary patient outcome data (evaluation) at facility, district,regional,andnationallevelsoveraperiodoftime.
6.2 TBRecordingandReportingToolsinChildren
RecordingandReportingofChildCases
Childrenwith TB should be included in routine recording and reporting. Notify allidentifiedTBcasesinchildrenandregisterthechildfortreatment.Ifsmearpositive,record their smear statusatmonths2,5andat theendof treatment.Record thechild’streatmentoutcomeaswell.
TB registers are available at facility and district levels. The district registers are inpaper and electronic version (in the DHIS2). The paper version is filled out at thedistrict,andthentranscribedintoelectronicversion.
TBFormsandCards
• TB01–TuberculosistreatmentcardThehealthcareworkerwhomanagesthepatient’streatmentfillsoutthiscardateverypatientvisit.Itfocusesonthediagnosisandclinicalaspectsofpatientcare.
• TB02–KadiyamgonjwawakifuakikuuThehealthcareworkerfillsoutthiscardwhentreatment isstarted. It iskeptby thepatient,providesevidenceofprevious treatmenthistory, andenablesthepatienttocollecttheirmedicines.
• TB03-TBUnitregister
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This register list of all patients taking TB drugs in the clinic. Data from thisregisterprovidethefoundationfortheDistrictTBregisterandformsthebasisfor major decisions. It is filled out by health care workers in TB clinics whoprovidedrugs,treatment,andcounsellingtopatients.
• TB04–TuberculosisdistrictregisterContainsthelistofallTBpatientsnotifiedinthedistrictandthetransferredinfromotherdistrict.
• TB05-TuberculosisLaboratoryRegisterThis is a laboratory registerwhere all sputum samples from presumptive TBcasesareregisteredincludingrespectivesputumexaminationresults.
• TB06-RequestandreportingformforTBcultureandDrugsusceptibilityTest• TB07-TuberculosisQuarterlyCaseNotificationReportForm• TB08-TuberculosisDrugsandSuppliesCalculationandOrderForm• TB09-TuberculosisQuarterlyTreatmentResultsReportForm§ TB11–Quarterlyreportoftreatmentresultsoftransferred-inTBandTB/HIV
patientsnotifiedinthequarterending12monthsearlier.
Communitybasedrecordingandreportingtools
• TB12-Fomuyawatu(wateja)waliofanyiwauchunguziwaawaliwaTBkatikaJamii
• TB13-RejestayaWanaohisiwakuwanaTBkatikaJamii• TB14-FomuyaTaarifayaRoboMwakayaKikundichaJamiichaHudumazaTB• TB15:FomuyarufaayahudumazaTBngaziyajamii
TBandLeprosycombinedforms
• TB/LEP01-RequestandReportFormforSmearExamination• TB/LEP02-FomuyaRufaa/Uhamisho
MDRTBtools
• MDRTB01:MDRTBTreatmentCard• MDRTB02:MDRTBPatientIdentityCard• MDRTB03:MDRTBSuspectRegister• MDRTB04:MDRTBDistrictRegister
HIVFormsandCards
• CTC1Card• CTC2Card• PreARTregister• ARTregister
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6.3 RecordingandReportingofOutcomesofChildTBCases
AssigningandEvaluatingTreatmentOutcomes
Healthworkersathealthfacilitylevelfillinthetreatmentoutcomesofeachpatientontreatmentcardandintheunitregister,theDTLCfillintreatmentoutcomeinthedistrictunitandcompilequarterly report fornotificationand treatmentoutcomes.TheNTLPcompilesallcasesandtreatmentoutcomedatafornationalrecordingandreportingpurposes.NewpatienthaveneverbeentreatedforTBorhavetakenanti-TBdrugsforlessthan1month.OutcomeassignmentisdonebytheDTLCorhealthcareworkerafter6monthsoftherapyasfollows:
• Treatment completed: A child with smear negative pulmonary TB or extra-pulmonary TB cases, who has completed treatment after 6 months ofcontinuoustherapy,or168doses.Thisincludes56dosesintheintensivephaseand 112 doses in the continuation phase. Since most children have sputumsmear negative and/or extra-pulmonary TB, it is impossible to showbacteriologicalcureandmostcaseswillbeclassifiedastreatmentcompleted.
• Cured:Newbacteriologically confirmedpatientswithnegative sputumsmearorcultureresultsat5monthsandonatleastonepreviousoccasion.However,patientshouldcomplete168doses(6monthsoftreatment).
• Treatment failed: New bacteriologically confirmed patients with positivesputum smear or culture results at 5 months or later during treatment.Requestasputumspecimen formycobacterial cultureanddrugsusceptibilitytesting (DST).Closetheir treatmentcard (outcome= failure)andopenanewtreatmentcard(typeofpatient=treatmentafterfailure).
Previouslytreatedpatientshavereceived1monthormoreofanti-TBdrugs inthepast.Outcomesforpreviouslytreatedarereportedsimilarasdescribedabove.
Table6.1.Definitionsoftreatmentoutcomes
Outcome Definition
Cured A PTB patientwith bacteriologically confirmed TB at the beginning oftreatmentandwhowassmearorculturenegativeinthelastmonthoftreatmentandonatleastonepreviousoccasion
Treatmentcompleted ATBpatientwhocompletedtreatmentwithoutevidenceoffailure,BUTthereisnorecordtoshowthatsputumsmearorcultureresultsinthelastmonth of treatment and on at least one previous occasion werenegative, eitherbecause theywerenotdoneorbecause resultswerenotavailable
TreatmentFailed ATBpatientwhosesputumsmearorculture ispositiveatmonth5orlaterduringtreatment.
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Died A TB patient who dies for any reason before starting or during thecourseoftreatment.
Losttofollow-up A TB patient who did not start treatment or whose treatment wasinterruptedfortwoconsecutivemonthsormore.
Notevaluated ATBpatientforwhomnotreatmentoutcomeisassigned.(Thisincludescases“transferred
out”toanotherregionandwhenthetreatmentoutcomeisunknowntothereportingdistrict.)
Treatmentsuccess Sumofcuredandtreatmentcompleted
AgedisaggregatedDataandIndicators
AgedisaggregatedData
Cohortanalysisisakeytoolforevaluatingprogrameffectiveness.Itisthereviewofthe outcomes for a cohort or group of patients that were started on treatmentduringthesametimeframe.TypeofTB,classificationandoutcomesforchildrenareanalyzedbasedonthefollowingagegroups:under5years,from5tounder10years,andfrom10tounder15years.
TB/HIVprogrammeindicators
TB/HIVprogrammeindicatorsareusedtoassesstheeffectivenessofTB/HIVprogrammecollaborationandintegration.Measurementoftheseindicatorscanalsoidentifyareasofpossibleprogrammestrengthening.
Table6.2.IndicatorsforNTLProutinerecordingandreporting
Indicator SignificanceProportionofchildrenwithTBamongstallTBcasesnotified
Mayindicateover-orunder-reportingofTBcasesinchildren
ProportionofchildrenwithpulmonaryTBamongstchildhoodTBcases
Mayindicateover-orunder-diagnosisofpulmonaryTB
ProportionofchildrenwithTBwhoarecuredamongstsmear-positive childhood TB cases (demonstrated byend-of-treatment smear conversion from positive tonegative)
DemonstratesthequalityofmanagementofchildrenwithTBintheprogram
Proportion of children who complete treatmentamongstsmear-positivechildhoodTBcases(thosewhocomplete a full course of anti-TB treatment in whomsmearconversionisnotdemonstrated)
DemonstratesthequalityofmanagementofchildrenwithTBintheprogram
Proportionofchildrenwhoaresuccessfullytreatedamongstsmear-positivechildhoodTBcases(cured+treatmentcompleted)
DemonstratesthequalityofmanagementofchildrenwithTBintheprogram
ProportionofchildrenwithmiliaryTBorTBmeningitisamongstchildhoodTBcases
ThisproportionshouldbeverylowwhereBCGvaccinationcoverageishigh
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TB contactsof index casesbeing treated for TB shouldbeentered into theTBcontact register. This register can serve as a reminder of the importance ofcontactscreeningaswellasprovideimportantinformationoncontacts,suchasage,HIVstatus,andmanagement.Arecordshouldbekepttoindicatecontactscreeninghastakenplaceandtheoutcomesdocumented.
TBclinicsettingindicators
• NumberandproportionofchildrencounselledandtestedforHIVamongstallchildrennotified.
• NumberandproportionofchildrenwhotestedHIVpositive.• Number and proportion of children who tested HIV positive and were
referredtoaCTC.• Number and proportion of children who tested HIV positive and were
registeredataCTC.• Number and proportion of children who tested HIV positive and were
initiatedonCPT.• Number and proportion of children who tested HIV positive and were
initiatedonART.
HIVclinicsetting• NumberandproportionofchildrennewlyenrolledinHIVcare.• NumberofchildrenscreenedforTBamongstnewlyenrolledinHIVcare.• NumberofchildrendiagnosedwithTBamongstnewlyenrolledinHIVcare.• NumberofchildreninitiatedonTBtreatmentamongstnewlyenrolledinHIV
care.• NumberofchildreninitiatedonIPTamongstnewlyenrolledinHIVcare
Figure6.1:DataFlowforTB
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KeyPoints
• Recording and reporting are essential to a facility’s success, as they helphealthcare
workersto:§ Assesspatientprogress§ Ensure quality of care, sharing of information between patient and
healthworkers§ Conductmonitoringandevaluationactivities§ Assessprogramperformance§ Planprograms§ Demonstrateaccountability
• Learning how to use all of the different TB data forms is key to successfulreporting
• Themoreaccurateandcompletereportingis,themorelikelyit isthathealthcareworkerswillmeetTBprogrammeobjectives.
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7 ROLESANDRESPONSIBILITIESOFTHEHEALTHSYSTEMINDIAGNOSISANDMANAGEMENTOFCHILDRENWITHTUBERCULOSIS
7.1 Introduction
Thediagnosis, treatment, and casemanagementof TB in children require thatcertainservicesareavailableatdifferent levelsofcare.Thedeliveryofservicesandtheresponsibilitiesofstaffwilldifferwithinthelevelsofcare.
7.2 CommunityLevelTBcare
CommunityTBcareapproachaimat involvingcommunitiesandcommunityhealthworkers including former TB patients to improve early TB care-seeking andtreatment adherence, increase community awareness around TB symptoms andsignsamongchildren,andmitigateTBstigma.TheresultingoutcomewillcontributetoincreasedchildhoodTBcasedetectionandtreatmentsuccess.
Community TB care represents a wide range of activities carried out at thecommunity level by community members themselves, in partnership withcommunityhealthcareworkerswhoserveasalinktothehealthcaresystem.Theseactivitiesinclude:
• RecognitionofsignandsymptomsofchildhoodTB• ToIdentifychildrenwithpresumptiveTBandreferorescortthemtohealth
facilities• ToEnsurereferralfeedbackfromhealthfacilities• ToEnsureallconfirmedTBcasesareinitiatedwithtreatment• Conductcontacttracing• Reducingstigmaanddiscriminationinthecommunitiesandwithinfamilies• Providingsupportandadvocatingfortreatmentadherence• IncreasingawarenessonchildhoodTBanddemandformanagement
7.3 HealthfacilitylevelTBcare
PrimaryhealthfacilitylevelofcareThislevelincludesdispensariesandhealthcentres.Atthislevel,staffshouldbeableto:• RecognisethesymptomsandsignsofchildhoodTB• Recognize the significance of household contact with smear-positive
indexcases• Diagnose children with presumptive TB by using Paediatric TB score
charts,AFBsmearorXpertMTB/Rif• Register immediately all children diagnosed with TB and start
treatmentunderDOTfollowingNTLPguidelines• Perform HIV counseling and testing following National guideline for
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managementofHIVandAIDS.• Do counselling on special issues related to children, including the
challengesofdisclosureofHIVserostatusatdifferentages
SecondarylevelofcareThislevelincludesdistrictandregionalhospitals.Atthislevel,staffshouldbetrainedandbeabletoperformallactivitiesattheprimaryhealthcarelevelasmentionedabove.Inadditionthefollowingactivitiesshouldbeperformed:• Tuberculinskintest(TST)• Lumbarpuncture,pleuraltapandascitestap,Sputuminductionand
gastriclavagetocollectsamplesforAFBsmearmicroscopy,XpertMTB/RIFandculture
• Readchestx-rays• Diagnose and manage complicated TB cases like meningitis,
osteoarticulardisease,anddrug-resistantTB.
TertiarylevelofcareThis level includes zonal and referral/consultant hospitals and specializedhospitals.Inadditiontotheactivitiesperformedatthesecondarylevel,atthislevel,servicesshouldinclude:• CultureandDST• Interferongammareleaseassay(IGRA)• Diagnosis and management of complicated TB cases, including drug-
resistantTBinchildren• Toensureinternalandexternalqualitycontroloftheaboveprocedures
atthelowerlevelsofcare
7.4 IntegrationofTBservicesintoReproductiveandChildHealthservices
AllchildrenuptotheageoffiveyearsarerequiredtoattendReproductiveandChild Health Clinic (RCH) for growth monitoring and immunization services.These clinics serve as the opportunity for TB screening in children as healthworkersintheseclinicsaremostlythefirsttorealizehealthissuesinchildrenandtheirmotherswhileattendingroutinevisits.LinkingTBserviceswithRCHserviceswillcontributeto increasedTBcasedetectionandtreatmentsuccessin children. Education on TB prevention, diagnosis and treatment should beincluded in pregnancy and child health care package. These services shouldincludethefollowing:• TBscreeningduringantenatal,natalandpostnatalperiod(motherand
infant), all those who screen positive should be referred forinvestigation/treatment
• TBscreeningforall<5yearsduringtheirvisits• Contact-tracingforpersonswithinfectiousTBintheirfamiliesandprovide
IPTprophylaxisforTBexposedinfantsandchildren• ProvidingTBtreatmentadherencesupport• HIVtestingandcounselingforTBpatients(parentsandchildren)• ProvisionofTBeducation,supervisionandsupportforstaffandvolunteers
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ANNEX1: SPUTUMINDUCTION
Sputuminductionisaprocedureinwhichtherespiratorytractisstimulatedtoproducesputumthroughtheuseof inhaledhypertonicsaline.Unlikegastricaspiration,sputuminduction isanaerosol-generatingprocedure.Therefore, thisprocedureshouldbeperformed inan isolationroom that has adequate infection control precautions (negative pressure, ultraviolet light[turnedonwhenroomisnotinuse],andanextractorfan).
Sputum induction is regarded as a low-risk procedure. Very few adverse events havebeenreported,andtheyincludecoughingspells,mildwheezing,andnosebleeds.Recentstudies have shown that this procedure can safely be performed even in infants asyoungas1monthold,thoughstaffwillneedtohavespecialisedtrainingandequipmenttoperformthisprocedureinsuchpatients.
Materialsneededforsputuminduction• Respiratory face mask (fit-tested N95 mask is recommended if available; N95mask
canbeusedbythesamepersonforupto1month)• Gloves • Nebuliser machine (with tubing and mask) • Suction machine with sputum trap • Inhaled bronchodilator (e.g., salbutamol inhaler) • Inhaled hypertonic saline(3-5%) • Suction catheter (soft, flexible, small caliber and large caliber) • Supplemental oxygen source • Log book/forms for the documentation of sputum induction procedure• Laboratory request form to accompany specimen to laboratory • Disinfectant solution (for disinfecting materials used) • Optional materials (should be used if available)
§ Fan(forairflow)§ Gogglesorvisor(foreyeprotection)§ Stethoscope§ Pulseoximeterorcardiacmonitor§ Nasopharyngealororalairways
Generalapproach
Examine children before the procedure to ensure they are well enough to undergo theprocedure.
Childrenwiththefollowingcharacteristicsshouldnotundergosputuminduction:• Inadequate fasting: If a child has not been fasting for atleast 3 hours, postpone the
procedureuntiltheappropriatetime.• Severe respiratory distress, including rapid breathing, wheezing, andhypoxia.• Intubated. • Bleeding: Low platelet count, bleeding tendency, severe nosebleeds (symptomatic or
plateletcount<50,000/mlblood).• Reduced level of consciousness. • History of significant asthma (diagnosed and treated by a clinician).
Procedure1. Positioningthechild:
a. Infants:bestheldinthefeedingposition(cradled,supine).b. Olderchildren:helduprightorsemi-uprightincaregiver’sarms.
2. Pre-procedure assessment: Verify adequate fasting (no liquids/solids within past 3hours),assurethatnoneofthecontraindications(listedabove)applytothechild,checkbaselinepulseandrespiratoryrate,andascultatethelungstoexcludewheezing.Ensureallequipmentisreadyandsetupproperly.
3. Intra-procedure monitoring—monitor for the following throughout the
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procedure:a. Increasedrespiratoryrateorrespiratorydistress(indrawing,nasalflaring,grunting).b. Profusesweating.c. Vomiting.Ifanyofthesesymptomsareseen,thesputuminductionshouldbeterminatedandthepatientneedstobeassessedbyaclinician.
4. Administerabronchodilator(e.g.,salbutamol)toreducetheriskofwheezing:a. Afterchildisseated(orincaregiver’sarms),applythemasktothechild.b. Turnonthenebulizerandhavethecaregiverkeepthemaskonthechild’sface.c. Administerthenebulisedbronchodilatorfor3-5minutes.
5. Administernebulisedhypertonicsaline(e.g.,3%NaCl):After3-5minutesofbronchodilatortherapy,add5-10mlofhypertonic saline to thenebuliser.
a. Administer nebulised hypertonic saline for 15minutes or until 5 cm3of solutionhasbeenfullyadministered.
b. Givechestphysiotherapyasnecessary;thisisusefultomobilizesecretions.c. Ifthechildbeginscoughingbeforethefull15minutesbuthasprovidedanadequate
specimen,thenitisokaytostopthesputuminduction.6. Suctioningofthesputum:
a. Thisisstartedafterthepatientbeginscoughing.b. Thereare3waystosuction:
1) Thesuctioncatheteralone(withoutanyairway)canbeinserteddirectly intothe nostril or mouth (where mucoid secretions are being produced) andsuctioned.
2) Nasopharyngealairway:Suctioncatheterisdippedinwaterandinsertedintonostril.Suctioncatheteristhenintroducedviathenasopharyngealairwayandairwayissuctioned.Cathetershouldbeinsertedtheapproximatelengthfromthechild’snostriltoearlobe.
3) Oropharyngealairway:Insertedintothechild’smouthtopreventclenchingofteethandbitingofcatheter.Thesuctioncatheteristhenintroducedintothemouthandtheairwayissuctioned.
c. When correctly inserted, the suction catheter should stimulate an involuntarycough.
d. Suctionbycoveringthesuctionholeonthecatheter/trapdevice.e. Start with negative pressure at 15-20mm Hg, and only increase the pressure if
needed to obtain an adequate sample. (Caution: Very high negative suctionpressurecancausetissuedamageandairwaybleeding.)
f. Anadequatesampleis2ml(ormore)ofthickmucoidsecretions.7. Post-procedureassessment:Monitor thechild for10minutes for increased respiratory
rate or increased respiratory distress (provide oxygen if this occurs, and evaluate byclinician).
Anyequipmentthatwillbereusedwillneedtobedisinfectedandsterilisedbeforeusewith a subsequent patient. Clean the tubing of the nebuliser machine in preparedantisepticsolution,wipedownthechair/equipmentwithaclothsoakedinantisepticsolution, and discard any disposable equipment. Wash hands at the end of eachencounter.
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ANNEX2: GASTRICASPIRATION
Gastric aspiration is used to collect gastric contents to try to confirm the diagnosis oftuberculosis (TB) by microscopy and mycobacterial culture in young children when sputumcannotbe spontaneouslyexpectoratednor inducedusinghypertonic saline.During sleep, thelung’smucociliarysystemsweepsmucusupintothethroat,whereitisswallowedandremainsinthestomachuntilthestomachempties.Therefore,thehighest-yieldspecimensareobtainedfirst thing in the morning. Gastric aspiration on each of 2consecutive mornings should beperformed for each patient. Performing the test properly usually requires two people (onedoingthetestandanassistant).Childrenwithalowplateletcountorbleedingtendencyshouldnotundergotheprocedure.
Requiredequipment1. Gloves2. Nasogastrictube(usually10Frenchorlarger)3. 5,10,20,or30cm3syringe,withappropriateconnectorforthenasogastrictube4. Litmuspaper5. Specimencontainer6. Pen(tolabelspecimens)7. Laboratoryrequisitionforms8. Sterilewaterornormalsaline(0.9%NaCl)9. Sodiumbicarbonatesolution(8%)10. Alcohol/Chlorhexidine
ProcedureTheprocedure can be carried out as an inpatient first thing in themorningwhen the childwakesup,atthechild’sbedside,orinaprocedureroomontheward(ifoneisavailable),orasanoutpatient(providedthatthefacilityisproperlyequipped).Thechildshouldhavefastedforatleast4hours(infantsfor3hours)beforetheprocedure.1. Prepareallequipmentbeforestartingtheprocedure.2. Positionthechildonhisorherbackorside.Theassistantshouldhelptoholdthechild.3. Measurethedistancebetweenthenoseandstomach,toestimatethedistancethatwill
berequiredtoinsertthetubeintothestomach.4. Attachasyringetothenasogastrictube.
5. Gentlyinsertthenasogastrictubethroughthenoseandadvanceitintothestomach.6. Withdraw (aspirate) gastric contents (2–5 ml) using the syringe attached to the
nasogastrictube.7. Tocheckthatthepositionofthetubeiscorrect,testthegastriccontentswithlitmuspaper:
blue litmus turns red (in response to the acidic stomach contents). (This can also becheckedbypushingsomeair[3–5ml]fromthesyringeintothestomachandlisteningwithastethoscopeoverthestomach.)
8. If no fluid is aspirated, insert 5–10 ml sterile water or normal saline and attempt toaspirateagain.
a. If still unsuccessful, attempt this again (even if the nasogastric tube is in an incorrectposition and water or normal saline is inserted into the airways, the risk of adverseeventsisstillverysmall).
b. Donotrepeatmorethanthreetimes.9. Withdrawthegastriccontents(ideallyatleast5–10ml).10. Transfergastricfluidfromthesyringeintoasterilecontainer(sputumcollectioncup).11. Add an equal volume of sodium bicarbonate solution to the specimen (in order to
neutralizetheacidicgastriccontentsandtopreventdestructionoftuberclebacilli).
Aftertheprocedure1. Wipethespecimencontainerwithalcohol/chlorhexidinetopreventcross-infectionand
labelthecontainer.
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2. Filloutthelaboratoryrequisitionforms.3. Transport the specimen (in a cool box) to the laboratory for processing as soon as
possible(within4hours).4. If it is likely to takemore than4hours for the specimen tobe transported,place it in the
refrigerator(4–8°C)andstoreuntiltransported.5. Givethechildhisorherusualfood.
SafetyGastric aspiration is generally not an aerosol-generatingprocedure. As young children arealso at low risk of transmitting infection, gastric aspiration can be considered a low-riskprocedure for TB transmission and can safely be performed at the child’s bedside or in aroutineprocedureroom.
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ANNEX3: DIAGNOSISANDMANAGEMENTOFMALNUTRITION
DiagnosisMalnutrition can be recognised by clinical manifestations of visible severe wasting (e.g.,cachexiaand/orpresenceofswellingofbothextremities).Tocheckforwasting,undressthechildandlookatthefrontandbackview:• Is the outline of the child’s ribs easily seen? • Does the skin of the upper arms look loose? • Does the skin of the thighs look loose? • Is flesh missing from the buttocks?
Tocheckforoedema,graspthefootsothatitrestsinyourhand,withyourthumbontopofthe foot. Press your thumb gently for a few seconds. The child has oedema if a pit (dent)remainsinthefootwhenyouliftyourthumb.Tobeconsideredasignofseveremalnutrition,oedemamustappearinbothfeet.
Theextentofoedemaiscommonlyratedasfollows:
+mild(grade1):bothfeetonly++moderate(grade2):bothfeet,pluslowerlegs,hands,orlowerarms+++severe(grade3):generalisedoedema,includingbothfeet,legs,hands,arms,andface
Oedemaisacharacteristicofkwashiorkor.
Malnutritionisconfirmedbyanthropometricmeasurementsasshowninthetablebelow.Diagnosticcriteriaformalnutritioninchildrenaged6to60months
Indicator/Measure*
Cutoff Severeacutemalnutrition Moderateacutemalnutrition
Weight-for-height/length Lessthan-3SD(<70%) Between-2SDand-3SD(70–79%)
Mid-upperarmcircumference Lessthan11.5cm 11.5–12.5cm Bilateraloedema(anytype) SD:standarddeviation.*Based on World Health Organization child growth standards, available atwww.who.int/childgrowth/standards.
Principlesofmanagement
It is importanttoaddressalltheproblemsfacingthechild. Inadditiontoundergoingoverallassessment, children with tuberculosis should undergo complete assessment of nutritionalstatus,includingthefollowing:• Detailed dietary history to identify the existence of any feeding problems and support
networks,includingresourcesavailableathomeforthefamily.• Generalexaminationfocusedonidentifyingfeaturesofmalnutrition,includingtaking
of accurate anthropometric measurements to identify the growth pattern andappropriatemanagementplan.
• Anindividualizednutritionalsupportplan,dependingontheseverityofmalnutritionandtheassociatedcomplications
Managementofsevereacutemalnutrition
Children who present with severe acute malnutrition (kwashiorkor, marasmus, or marasmic-kwashiorkor) and with any of the following complications need inpatient care immediately forstabilisationandinitialmanagementusingtheTanzanianNationalGuidelinesforManagementof AcuteMalnutrition for the inpatient management of severe acute malnutrition (i.e., the tenstepsforrecovery): • Severe oedema (bilateral pitting oedema, grade3). • Anorexia.
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• Not alert (lethargic/unconscious). • Severe co-morbid disease conditions.
Children with severe acute malnutrition without complications who are alert with a goodappetitecanbemanagedonanoutpatientbasisusingready-to-eat therapeutic food (RUTF)andbasicmedicalcare.(ThesechildrenaregivenaportionofRUTF,encouragedtoeatit,andpassthetestiftheyfinishthefeed.)• Provide200Kcal/kg/dayRUTF.• Prescribebroad-spectrumantibiotics(e.g.,amoxicillin)for1week.• Conductweeklyor2-weeklyfollow-upsforassessmentandrefillofRUTFduringtheintensivephase, followed by long- term follow-up at 4-weekly intervals until the child recoverssatisfactorily(weight-for-heightisapproximately90percentofthestandard).
Managementofmoderatemalnutrition
Children with moderate malnutrition are managed on an outpatient basis by providing anindividualplantoimprovedietaryintakedependingontheresourcesavailabletothefamily.This translates into providing an extra meal in addition to the recommended age-specificfeedings. Adding a spoon of oil and differentmixes of food including fruits and vegetablesincreasestheenergydensityofmealsandthevariousnutrientsrequiredforcatch-upgrowth.RUTFsupplementscanalsobeprovided.Long-termfollow-upat4-weeklyintervalsshouldbeconducted until the child recovers satisfactorily (weight-for-height is approximately 90percentof the standard).Themother’scardcanbeused to counselon feedingand feedingproblems.
Managementalgorithmforacutemalnutrition
IMCI: integrated management of childhood illness; MUAC: mid-upper armcircumference;SD:standarddeviation.
With complications Without complications
ACUTE MALNUTRITION
Severe malnutrition Oedema (+/++/+++)
Poorappetite
Inpatient therapeutic
malnourished children (70–79% [between
Severe malnutrition
Go
70–79% (between
Goodappetite Clinicallywell
Community-based
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ANNEX4: DrugRe-introductionChallengefollowingdrug-inducedhepatitisforchildrenbasedonweight-bands
WeightBand:0-3.9kg**Seekspecialistassistancefor<4kgweightband**
WeightBand:4-7.9kgIsoniazid
(usingpaediisoniazid100mgtablets)
Day1 Day2 Day3 Day4
25mg(¼tablet)
50mg(½tablet)
75mg(¾tablet)
100mgfulldose(1tablet)
Rifampicin(usingpediRH75/50
tablets)
Day5 Day6 Day7 Day818.75mg(¼tablet)
37.5mg(½tablet)
56.25mg(¾tablet)
75mgfulldose(1tablet)
Pyrazinamide(usingpaediRHZ
75/50/150tablets)
Day9 Day10 Day11 Day1237.5mg(¼tablet)
75mg(½tablet)
112.5mg(¾tablet)
150mgfulldose(1tablet)
Ethambutol(usingpaediethambutol
100mgtablets)
Day13 Day14 Day15 Day1625mg
(¼tablet) 50mg
(½tablet) 75mg
(¾tablet) 100mgfulldose
(1tablet) WeightBand:8-11.9kg
Isoniazid(usingpaediisoniazid
100mgtablets)
Day1 Day2 Day3 Day4
50mg(½tablet)
100mg(1tablet)
150mg(1.5tablets)
200mgfulldose(2tablets)
Rifampicin(usingpaediRH75/50
tablets)
Day5 Day6 Day7 Day837.5mg(½tablet)
75mg(1tablet)
112.5mg(1.5tablets)
150mgfulldose(2tablets)
Pyrazinamide(usingpaediRHZ75/50/150tablets)
Day9 Day10 Day11 Day1275mg
(½tablet)150mg(1tablet)
225mg(1.5tablets)
300mgfulldose(2tablets)
Ethambutol(usingpaediethambutol
100mgtablets)
Day13 Day14 Day15 Day1650mg
(½tablet)100mg(1tablet)
150mg(1.5tablets)
200mgfulldose(2tablets)
WeightBand:12-15.9kgIsoniazid
(usingpaediisoniazid100mgtablets)
Day1 Day2 Day3 Day4
50mg(½tablet)
100mg(1tablet)
200mg(2tablets)
300mgfulldose(3tablets)
Rifampicin(usingpaediRH75/50
tablets)
Day5 Day6 Day7 Day837.5mg(½tablet)
75mg(1tablet)
150mg(2tablets)
225mgfulldose(3tablets)
Pyrazinamide(usingpaediRHZ75/50/150tablets)
Day9 Day10 Day11 Day1275mg
(½tablet)150mg(1tablet)
300mg(2tablets)
450mgfulldose(3tablets)
Ethambutol(usingpaediethambutol
100mgtablets)
Day13 Day14 Day15 Day1650mg
(½tablet)100mg(1tablet)
200mg(2tablets)
300mgfulldose(3tablets)
WeightBand:16-24.9kgIsoniazid
(usingpaediisoniazid100mgtablets)
Day1 Day2 Day3 Day4
100mg(1tablet)
200mg(2tablet)
300mg(3tablets)
400mgfulldose(4tablets)
Rifampicin(usingpaediRH75/50
tablets)
Day5 Day6 Day7 Day875mg
(1tablet)150mg(2tablet)
225mg(3tablets)
300mgfulldose(4tablets)
Pyrazinamide(usingpaediRHZ75/50/150tablets)
Day9 Day10 Day11 Day12150mg(1tablet)
300mg(2tablet)
450mg(3tablets)
600mgfulldose(4tablets)
Ethambutol Day13 Day14 Day15 Day16
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(usingpaediethambutol100mgtablets)
100mg(1tablet)
200mg(2tablet)
300mg(3tablets)
400mgfulldose(4tablets)
H:isoniazid;R:rifampicin;Z:pyrazinamide.*Alwaysdoseanti-TBdrugsinchildrenbasedonweight.
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ANNEX5: DIAGNOSISOFHIVINFECTIONININFANTSANDCHILDRENLESSTHAN18MONTHS
DiagnosisofHIVinfectionininfants All infants born of HIV-infected women have passively transferredmaternal HIV antibodies that persistuntil 9 to 18 months of age. These antibodies make interpretation of positive antibodytestsdifficultinchildrenyoungerthan18months.Assaysthatdetectthevirusoritscomponents(i.e.,virologictests)arerequiredinordertopositivelydiagnoseHIVinfectioninchildrenyoungerthan18monthsofage.The twomostcommonlyused tests forsuchadiagnosisareDNAorRNApolymerasechainreaction(PCR).
PCRtestsshouldbedoneat4to6weeksoratthesecondreproductiveandchildhealthvisit(i.e.,8weeksafterdelivery):• Forachildwhowasneverbreastfed,asinglenegativePCRtestaftertheageof4weeksexcludesHIV
infection.• Forachildwhowasweaned formore than6weeksprior tovirologic (DNAPCR) testing, a
negativePCRtestexcludesHIVinfection.• Ifthechildisbeingbreastfed,anegativevirologictestdoesnotexcludeinfection.Ongoingexposure
to HIV through breastfeeding continues to put the child at risk of infection. Confirmatory testingshouldbedone6weeksaftercompletecessationofbreastfeedingwithDNAPCRasdescribedabovetodeterminefinalinfectionstatus.
Childrenbetweentheagesof9and18monthsat the firsthealthencountershouldhavearapidHIVantibodytestsincematernalHIVantibodiesdiminishrapidlybetween9and18monthsofage.AllpositivetestsshouldbeconfirmedwithaDNAPCRtest.Iftheantibodytestisnegativeandtheinfantisstillbreastfeeding,theantibodytestshouldberepeatedatleast12weeksaftercompletecessationofbreastfeeding.However, if the child has a positive rapid HIV antibody test and is symptomatic, fulfillingWorld HealthOrganization stage3 or4 criteria, andvirologic tests arenot availablebutHIVantibodies arepresent,apresumptive diagnosis should be made and antiretroviral therapy started. In these children,confirmatorytestingwitheither1)virologictestsassoonaspossibleor2)HIVantibodytestsat18monthsage must be performed. However, initiation of ART should not be delayed while waiting confirmatorytesting.
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DiagnosisofHIVInfectionininfantsandyoungchildrenlessthan18monthsofage
AdaptedfromUnitedRepublicofTanzaniaMoHSWNACPNationalGuidelinesfortheManagementofHIVandAIDS.May,2015.5thEdition.
ART:antiretroviraltherapy;PCR:polymerasechainreaction;BF:breastfeeding.
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